Month: April 2016

[Anatomy] Motor Pathways

April 30, 2016 Anatomy, Neurology No comments , , , , , , , , , ,

Screen Shot 2016-04-30 at 3.31.56 PMSomatosensory Pathways

Motor pathways are formed from the cerebral nuclei, the cerebllum, descending projection tracts, and motor neurons. Descending project tracts are motor pathways that originate from the cerebral cortex and brainstem. There are at least two motor neurons in the somatic motor pathway: an upper motor neuron and a lower motor neuron. Motor neurons within these tracts either synapse directly on motor neurons in the CNS or on interneurons that, in turn, synapse on motor neurons. The cell body of an upper motor neuron is housed within either the cerebral cortex or a nucleus within the brainstem. Axons of the upper motor neuron synapse either directly on lower motor neurons or on interneurons that synapse directly on lower motor neurons. The cell body of a lower motor neuron is housed either within the anterior horn of the spinal cord or within a brainstem cranial nerve nucleus. Axon of the lower motor neurons exit the CNS and project to the skeletal muscle to be innervated.

Motor neuron axons form two types of somatic motor pathways: direct pathways and indirect pathways. The direct pathways are responsible for conscious control of skeletal muscle muscle activity, and the indirect pathways are responsible for unconscious control of skeletal muscle activity.


Direct Pathway

The direct pathway originates in the pyramidal cells of the primary motor cortex. Their axons project either into the brainstem or into the spinal cord to synapse directly on lower motor neurons. The axons from pyramidal cell upper motor neurons descend through the internal capsule, enter the cerebral peduncles, and ultimately form two descending motor tracts of the direct pathway: corticobulbar tracts and corticospinal tracts.

Corticobulbar Tracts (upper motor neurons + lower motor neurons)

The corticobulbar tracts originate from the facial region of the motor homunculus within the primary motor cortex. Axons of these upper motor neurons extend to the brainstem, where they synapse with lower motor neuron cell bodies that are housed within brainstem cranial nerve nuclei. Axons of these lower motor neurons help form the cranial nerves. The corticobulbar tracts transmit motor information to control the following movements:

  • Eye movement (via CN III, IV, and VI)
  • Cranial, facial, pharyngeal, and laryngeal muscles (via CN V, VII, IX, and X)
  • Some superficial muscles of the back and neck (via CN XI)
  • Intrinsic and extrinsic tongue muscles (via CN XII)

Corticospinal Tracts (upper motor neurons + lower motor neurons)

Screen Shot 2016-04-30 at 3.34.15 PMThe corticospinal tracts descend from the cerebral cortex through the brainstem and form a pair of thick anterior bulges in the medulla oblongata called the pyramids. Then they continue into the spinal cord to synapse on lower motor neurons in the anterior horn of the spinal cord. The corticospinal tracts are composed of two components: lateral and anterior corticospinal tracts. The lateral corticospinal tracts include about 85% of the axons of the upper motor neurons that extend through the medulla oblongata. They decussate within the pyramids of the medulla oblongata and then form the lateral corticospinal tracts in the lateral funiculi of the spinal cord. These tracts contain axons that innervate both lower motor neurons of the anterior horn of the spinal cord and interneurons within the spinal cord. Axons of the lower motor neurons innervate skeletal muscles that control skilled movement in the limbs. The anterior corticospinal tracts represent the remaining 15% of the axons of upper motor neurons that extend through the medulla oblongata. The axons of these neurons do not decussate at the level of the medulla oblongata. Instead, they remain on their original side of the CNS and descend ipsilaterally, meaning "on the same side", to form the anterior corticospinal tracts in both anterior white funiculi. At each spinal cord segment, some of these axons decussate through the median plane in the anterior white commissure. After crossing to the opposite side, they synapse either with interneurons or lower motor neurons in the anterior horn of the spinal cord. Axons of the lower motor neurons innervate axial skeletal muscle.

 


Indirect Pathway

Several nuclei within the midbrain initiate motor commands for activities that occur at unconscious level. These nuclei and their associated tracts constitute the indirect pathway, so named because upper motor neurons originate within brainstem nuclei (that is, they are not pyramidal cells in the cerebral cortex). The axons of the indirect pathway take a complex, circuitous route before finally conducting the motor impulse into the spinal cord. Motor impulses conducted by axons of the motor, sensory, and association cortical areas, as well as input from the limbic system. Most of the output from cerebral nuclei goes to the primary motor cortex; cerebral nuclei do not exert direct control over lower motor neurons. Cerebral nuclei provide the patterned background movements needed for conscious motor activities by adjusting the motor cammands issued in other nuclei.


Role of the Cerebellum

The cerebellum plays a key role in movement by regulating the functions of the motor pathways. The cerebellum continously receives convergent input from the various sensory pathways and from the motor pathways themselves. In this way, the cerebellum unconsciously perceives the state of the body, receives the plan for movement, and then follows the activity to see if it was carried out correctly. When the cerebellum detects a disparity between the intended and actual movement, it may generate an error-correting signals. This singal is transmitted to both the premotor and primary motor cortices via the thalamus and the brainstem. Descending pathways then transmit these error-correting signals to the motor neurons. Thus, the cerebellum influences and controls movement by indirectly affecting the excitability of motor neurons.


Appendix

Corticospinal tract

Write Again – Receptor Rationale – Pharmacodynamics

April 22, 2016 Pharmacodynamics, Pharmacology No comments , , , , , , , , , , , , , , , , , , , ,

Screen Shot 2016-08-23 at 8.19.15 PMType of Drug Receptors

The effects of must drugs result from their interaction with macromolecular components of the organism. These interactions alter the function of the pertinent component and initiate the biochemical and physiological changes that are characteristic of the response to the drug. The term drug receptor or drug target denotes the cellular macromolecule or macromolecular complex with which the drug interacts to elicit a cellular response, i.e., change in cell function.

From a numerical standpoint, proteins form the most important class of drug receptors. Examples include the receptors for hormones, growth factors, transcription factors, and neurotransmitters; the enzymes of crucial metabolic or regulatory pathways; proteins involved in transport processes; secreted glycoproteins; and structural proteins. Specific binding of drugs to other cellular constituents such as DNA is also exploited for therapeutic purposes.

Drugs commonly alter the rate or magnitude of an intrinsic cellular response rather than create new responses. Drug receptors are often located on the surface of cells, but may also be located in specific intracellular compartments such as the nucleus. Many drugs also interact with acceptors (e.g., serum albumin) within the body. Acceptors are entities that do not directly cause any change in biochemical or physiological response. However, interactions of drugs with acceptors such as serum ablumin can alter the pharmacokinetics of a drug's action.

A major group of drug receptors consists of proteins that normally serve as receptors for endogenous regulatory ligands. These drug targets are termed physiological receptors. Many drugs act on physiological receptors and are particularly selective because physiological receptors have evolved to recognize and respond to individual signaling molecules with great selectivity.

Type of Drugs – From Perspective of Pharmacodynamics

Drugs that bind to physiological receptors and mimic the regulatory effects of the endogenous signaling compounds are termed agonists. If the drug binds to the same recognition site as the endogenous agonist the drug is said to be primary agonist. Allosteric (allotopic) agonists bind to a different region on the receptor referred to as an allosteric or allotopic site.

Drugs that block or reduce the action of an agonist are termed antagonists. Antagonism most commonly results from competition with an agonist for the same or overlapping site on the receptor (a syntopic interaction, or "primary" antagonism, or competitive antagonism), but can also occur by interacting with other sites on the receptor (allosteric antagonism), by combining with the agonist (chemical antagonism), or by functional antagonism by indirectly inhibiting the cellular or physiological effects of the agonist.

Agents that are only partly as effective as agonists regardless of the concentration employed are termed partial agonists.

Many receptors exhibit some constitutive activity in the absence of a regulatory ligand; drugs that stabilize such receptors in an inactive conformation are termed inverse agonists.

Drug Specificity

The chemical structure of a drug contributes to the drug's specificity. A drug that interacts with a single type of receptor that is expressed on only a limited number of differentiated cells will exhibit high specificity. If, however, a receptor is expressed ubiquitously on a variety of cells throughout the body, drugs acting on such a widely expressed receptor will exhibit widespread effects, and could produce serious side effects or toxicities if the receptor serves important functions in multiple tissues.


Quantitative Aspects of Drug Interactions with Receptors

Screen Shot 2016-04-18 at 8.36.23 PMReceptor occupancy theory asumes that response emanates from a receptor occupied by a drug, a concept that has its basis in the law of mass action. The basic currency of receptor pharmacology is the dose-response (or concentration-response) curve, a depiction of the observed effect of a drug as a function of its concentration in the receptor compartment. Figure 3-2 shows a typical dose-response curve; it reaches a maximal asymptotic value when the drug occupies all the receptor sites.

In general, the drug-receptor interaction is characterized by 1.binding of drug to receptor and 2.generation of a response in a biological system, as illustrated in Equation 3-1 where the drug or ligand is denoted as L and the inactive receptor as R. The first reaction, the reversible formation of the lignad-receptor complex LR, is governed by the chemical property of affinity. LR* is produced in produced in proportion to [LR] and leads to a response. This simple relationship illustrates the reliance of the affinity of the ligand (L) with receptor (R) on both the forward or association rate (k+1) and the reverse or dissociation rate (k-1). At any given time, the concentration of ligand-receptor complex [LR] is equal to the product of k+1[L][R], the rate of formation of the bi-molecular complex LR, minus the product k-1[LR], the rate dissociation of LR into L and R. At equilibrium, k+1[L][R] = k-1[LR]. Because the equilibrium dissociation constant (KD) is then described by ratio of the off and on rate constants (KDk-1/k+1), thus at equilibrium KD = k-1/k+1 = [L][R] / [LR] (Equation 3-2).

Screen Shot 2016-04-18 at 9.04.40 PMThe affinity constant or equilibrium association constant (KA) is the reciprocal of the equilibrium dissociation constant (KA = 1/KD); thus a high-affinity drug has a low KD and will bind a greater number of receptor at a low concentration than a low concentration than a low-affinity drug. As a practical matter, the affinity of a drug is influenced most often by changes in its off-rate (k-1) rather than its on-rate (k+1).

Screen Shot 2016-04-18 at 9.20.47 PMEquation 3-2 permits us to write an expression of the fractional occupancy (f) of receptors by agonist, Equation 3-3. This can be expressed in terms of KA (or KD) and [L]: f = [L]/([L] + KD). This relationship illustrate that under the condition of equilibrium and when the concentration of drug equals the KD, f = 0.5, that is, the drug will occupy 50% of the receptors. Note that this relationship describes only receptor occupancy, not the eventual response that is often amplified by the cell.

  • Occupation 

The second reaction shown in Equation 3-1 is the reversible formation of the active ligand-receptor complex, LR*. The ability of a drug to activate a receptor and generate a cellular response is a reflection of its efficacy. A drug with high efficacy may be a full agonist, eliciting, at some concentration, a full response. A drug with a lower efficacy at the same receptor may not elicit a full response at any dose. When it is possible to describe the relative efficacy of drugs at a particular receptor, a drug with a low intrinsic efficacy will be a partial agonist. A drug that binds to a receptor and exhibit zero efficacy is an antagonist. When the response of an agonist is measured in a simple biological system, the apparent dissociation constant, Kapp, is a macroscopic equilibrium constant that reflects both the ligand binding equilibrium and the subsequent equilibrium that results in the formation of the active receptor LR*.

Potency and Efficacy

Agonist

When the relative potency of two agonists of equal efficacy is measured in the same biological system, and downstream signaling events are the same for both drugs, the comparison yields a relative measure of the affinity and efficacy of the two agonists (Figure 3-3). It is convenient to describe agonist response by determining the half-maximally effective concentration (EC50) for producing a given effect. Thus, measuring agonist potency by comparison of EC50 values is one method of measuring the capability of different agonists to induce a response in a test system and for predicting comparable activity in another. Another method of estimating agonist activity is to compare maximal asymptotes in systems where the agonists do not produce maximal response (Figure 3-3B). The advantage of using maxima is that this property depends solely on efficacy, whereas drug potency is a mixed function of both affinity and efficacy.Screen Shot 2016-04-22 at 7.52.20 PM

PS: Potency refers to the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect.

Antagonist

For antagonists, characteristic patterns of antagonism are associated with certain mechanisms of blockade of receptors. One is straightforward competitive antagonism, whereby a drug with affinity for a receptor but lacking instrinsic efficacy competes with the agonist (i.e., endogenous ligands) for the primary binding site on the receptor. The characteristic pattern of such antagonism is the concentration-dependent production of a parallel shift to the right of the agonist dose-response curve with no change in the maximal response. The magnitiude of the rightward shift of the curve depends on the concentration of the antagonist and its affinity for the receptor. A partial agonist similarly can compete with a "full" agonist for binding to the receptor. However, increaseing concentrations of a partial agonist will inhibit response to a finite level characteristic of the drug's intrinsic efficacy; in contrast, a competitive antagonist will reduce the response to zero. Partial agonists thus can be used therapeuticallu to buffer a response by inhibiting excessive receptor stimulation without totally abolishing receptor stimulation.

An antagonist may dissociate so slowly from the receptor that its action is exceedingly prolonged, as with the opiate partial agonist buprenorphine and the Ca2+ channel blocker amlodipine. In the presence of a slowly dissociating antagonist, the maximal response to the agonist (i.e., endogenous ligand) will be depressed at some antagonist concentrations. Operationally, this is referred to as noncompetitive antagonism, although the  molecular mechanism of action really cannot be inferred unequivocally from the effect. An antagonist may also interact irreversibly (covalently) with a receptor to produce relatively irreversible effects. Noncompetitive antagonism antagonism can also be produced by another type of drug, referred to as an allosteric or allotopic antagonist. This type of drug produces its effect by binding to a site on the receptor distinct from that of the primary agonist, thereby changing the affinity of the receptor for the agonist. In the case of an allosteric antagonist, the affinity of the receptor for the agonist is decreased by the antagonist. In contrast, a drug binding at an allosteric site could potentiate the effects of primary agonists; such as drug would be referred to as an allosteric agonist or co-agonist.

Reflexes

April 22, 2016 Anatomy, Neurology, Physiology and Pathophysiology No comments , , , , , , , , , , , ,

Reflex are rapid, automatic, involuntary reactions of muscles (cardiac, smooth, and skeleton) or glands to a stimulus. All reflexes have similar properties:

  • A stimulus is required to initiate a response to sensory input.
  • A rapid response requires that few neurons be involved and synaptic delay be minimal.
  • A preprogrammed response occurs the same way every time.
  • An involuntary response requires no intent or pre-awareness of the reflex activity. Thus, reflexes are usually not suppressed. Awareness of the stimulus occurs after the reflex action has been completed, in time to correct or avoid a potentially dangerous situation.

An example of a reflex occurs when you accidentally touch a hot burner on a stove. Instantly and automatically, you remove your hand from the stimulus, even before you are completely aware that your hand was touching something extremely hot. A reflex is a survival mechanism; it allows us to quickly respond to a stimulus that may be dtrimental to our well-being without having to wait for the brain to process the information.

Components of a Reflex Arc

A reflex arc is the neural "wiring" of a single reflex. It always begins at a receptor in the PNS, communicates with the CNS, and ends at a peripheral effector, such as a muscle or gland cell. The number of intermediate steps varies, depending on the complexity of the reflex. Generally, five steps are involved in a simple reflex arc, including:

  • Stimulus activates receptor. Sensory receptors (dendritic endings of a sensory of a sensory neuron) respond to both external and internal stimuli, such as temperature, pressure, or tactile changes.
  • Nerve impulse travels through sensory neuron to the CNS. Sensory neurons conduct impulses from the receptor into the spinal cord.
  • Information from nerve impulse is processed in the integration center by interneurons. More complex reflexes may use a number of interneurons within the CNS to integrate and process incoming sensory information and transmit information to a motor neuron. Sensory information is also sent to the brain through interneuron collaterals. The simplest reflexes do not involve interneurons; rather, the sensory neuron synapses directly on a motor neuron in the anterior gray horn of the spinal cord.
  • Motor neuron transmits nerve impulse to effector. An effector is a peripheral target organ that responds to the impulse from the motor neuron. The motor neuron transmits a nerve impulse through the anterior root and spinal nerve to the peripheral effector organ.
  • Effector responds to nerve impulse from motor neuron. The effector response is intended to counteract or remove the original stimulus.

Reflex arcs may be ipsilateral or contralateral. A relfex arc is termed ipsilateral when both the receptor and effector organs of the reflex are on the same side of the spinal cord. A reflex arc is contralateral when the sensory impulses from a receptor organ cross  over through the spinal cord to activate effector organs in the opposite limb.

Reflexes also may be monosynaptic or polysynaptic. A monosynaptic reflex is the simplest of all reflexes. The sensory axons synapse directly on the motor neurons, whose axons project to the effector. Interneurons are not involved in processing this reflex. Very minor synaptic delay is incurred in the single synapse of this reflex arc, resulting in a very prompt reflex response. Polysynaptic reflexes have more complex neural pathways that exhibit a number of synapses involving interneurons within the reflex arc. Because this reflex arc has more components, there is a more prolonged delay between stimulus and response.

Autonomic Reflexes

The autonomic nervous system helps maintain homestasis through the involuntary activity of autonomic reflexes, also termed visceral reflexes. Autonomic reflexes consist of smooth muscle contractions, cardiac muscle contractions, or secretion by glands that are mediated by autonomic reflex arcs in response to a specific stimulus. A classic autonomic reflex involves the reduction of blood pressure. When an individual has elevated blood pressure, streth receptors in the walls of large blood pressures are stimulated. Impulses from these stretch receptors then travel through visceral sensory neurons to the cardiac center in the medulla oblongata. This leads to parasympathetic input to the pacemaker of the heart, resulting in a decrease in heart rate and a concomitant decrease in blood pressure. Autonomic reflexes are comparable to spinal reflexes because they involve a sensory receptor, sensory neurons, interneurons in the CNS, motor neurons, and effector cells.

Pancreatic Secretion and Its Regulation

April 17, 2016 Gastroenterology, Physiology and Pathophysiology No comments , , , , , , , ,

Overall View of Pancreatic Secretion Regulation

Pancreatic secretory activity related to meal ingestion occurs in cephalic (20-25%), gastric (10%), and intestinal phases (~60-70%). Pancreatic secretion is activated by a combination of neural and hormonal effectors. During the cephalic and gastric phases, secretions are low in volume with high concentrations of digestive enzymes, reflecting stimulation primarily of acinar cells. This stimulation arises from cholinergic vagal input during the cephalic phase, and vago-vagal reflexes activated by gastric distension during the gastric phase. During the intestinal phase, on the other hand, ductular secretion is strongly activated, resulting in the production of high volumes of pancreatic juice with decreased concentrations of protein, although the total quantity of enzymes secreted during this phase is actually also markedly increased. Ductular secretion during this phase is driven primarily by the endocrine action of secretin on receptors localized to the basolateral pole of duct epithelial cells. The inputs to the acinar cells during the intestinal phase include CCK and 5-HT from the intestine as well as neurotransmitters including ACh and GRP. The large magnitude of the intestinal phase is also attributable to amplification by so-called enteropancreatic reflexes transmitted via the enteric nervous system.

  • Cholinergic vagal input – cephalic phase – acinar secretion
  • Vago-vagal reflexes – gastric phase – acinar secretion
  • Secretin – intestinal phase – ductular (cells) secretion
  • CCK (via vago-vagal reflexes and non-ACh neurotransmitters) by CCK-RP and monitor peptide – intestinal phase – acinar cells
  • 5-HT (via vago-vagal reflexes) – intestinal phase – acinar cells
  • ACh – cephalic, gastirc, and intestinal phases – acinar cells
  • GRP – cephalic, gastirc, and intestinal phases – acinar cells
  • Enteropancreatic reflexes transmitted via the enteric nervous system – intestinal phase – ?

Mechanisms of Regulation of Pancreatic Secretion (Primarily the Intestinal Phase)

CCK

CCK can be considered a master regulator of the duodenal cluster unit, of which the pancreas is an important component. CCK is a potent stimulus of acinar secretion, acting predominantly via CCK1 receptor-dependent stimulation of vagal afferents close to its site of release in the duodenum, thereby evoking vago-vagal reflexes that stimulate acinar cell secretion via cholinergic and non-cholinergic neurotransmitters (GRP, VIP). Threre are also CCK1 receptors on the basolateral pole of acinar cells, but it now seems likely that these are only activated if circulating concentrations of CCK rise to supraphysiologic levels.

In addition to its effects on the pancreas, CCK coordinates the activity of other GI seggments and draining organ, including by contract the gallbladder, relaxing the sphincter of Oddi, and slowing gastric motility to retard gastric emptying and thereby control the rate of delivery of partially digested nutrients to more distal segments of the gut. Finally, CCK can modulate the activity of other neurohumorla regulators in a synergistic fashion. For example, CCK itself is a weak agonist of pancreatic ductular secretion of bicarbonate, but it markedly potentiates the effect of secretin on this transport mechanism.

CCK is synthesized and stored by endocrine cells located predominantly in the duodenum, labeled in some sources as "I" cells. Control of CCK release from these cells is carefully regulated to match the body's needs for CCK bioactivity. In part, this is accomplished by the activity of two luminally active CCK releasing factors, which are small peptides. One of these peptides is derived from cells in the duodenum, called CCK-releasing peptide (CCK-RP). It is likely release into the lumen in response to specific nutrients, including fatty acids and hydrophobic amino acids. The other luminal peptide that controls CCK secretion is monitor peptide, which is a product of pancreatic acinar cells. Release of monitor peptide can be neurally mediated, including by the release of ACh and GRP in the vicinity of pancreatic acinar cells during the cephalic phase, and mediated by subsequent vago-vagal reflexes during the gastric and intestinal phases of the response to a meal. Likewise, once CCK release has been stimulated by CCK-RP, it too can cause monitor peptide release via the mechanisms of vago-vagal reflexes.

When meal proteins and oligopeptides are present in the lumen in large  quantities, they compete for the action of trypsin and other proteolytic enzymes, meaning that CCK-RP and monitor peptide are degraded only slowly. Thus, CCK release is sustained, causing further secretion of proteases and other components of the pancreatic juice. On the other hand, once the meal has been fully digested and absorbed, CCK-RP and monitor peptide will be degraded by the pancreatic proteases. This then lead to the termination of CCK release, and thus a marked reduction in the secretion of pancreatic enzymes.

  • CCK-RP by duodenum cells
  • Monitor peptide by acinar cells

5-HT

5-HT, released from intestinal enterochromaffin cells in response to nutrients, activates a vagovagal reflex that mirrors and augments that of CCK itself. It has been calculated that CCK and 5-HT are each responsible for about 50% of pancreatic enzyme secretion during the intestinal phase.

Secretin

The other major regulator of pancreatic secretion is secretin, which is released from S cells in the duodenal mucosa. When the meal enters the small intestine from the stomach, the volume of pancreatic secretions increases rapidly, shifting from a low-volume, protein-rich fluid to a high volume secretion in which enzymes are present at lower concentrations (although in greater absolute amounts, reflecting the effect of CCK and neural effectors on acinar cell secretion). As the secretory rate rises, the pH and bicarbonate concentration in the pancreatic juice rises, with a reciprocal fall in the concentration of chloride ions. These latters effects on the composition of the pancreatic juice are mediated predominately by the endocrine mediator, secretin.

The S cells in the duodenal mucosa can be considered to act functionally as pH meters, sensing the acidity of the luminal contents. As the pH falls, due to the entry of gastric acid, secretin is released from the S cells and travels through the bloodstream to bind to receptors on pancreatic duct cells, as well as on epithelial cells lining the bile ducts and the duodenum itself. These cells, in turn, are stimulated to secrete bicarbonate into the duodenal lumen, thus causing a rise in pH that will eventually shut off secretin release. The pancreas is quantitatively the most important in the bicarbonate secretory response, although the ability of duodenal epithelial cells to secrete bicarbonate may be critically important to protect them from gastric acid, especially in the first part of the duodenum, which is proximal to the site of entry of the pancreatic juice and bile. In fact, patients suffering from duodenal ulcers have abnormally low levels of duodenal bicarbonate secretion both at rest and in response to luminal acidification.

The threshold for secretin release appears to be a luminal pH of less than 4.5. The mechanism by which the S cells sense the change in luminal acidity, and whether secretin release requires a peptide releasing factor and/or the function of mucosal sensory nerve endings is currently unclear. However, while other meal components, such as fatty acids, have been shown in experimental studies to evoke secretin release, the response to acid appears to be the most important physiologically. Subjects who are unable to secrete gastric acid (achlorhydric) secondary to disease or the administration of proton pump inhibitors, or in whom gastric contents have been neutralized by the oral administration of bicarbonate, fail to release secretin postprandially no matter what type of meal is given.

[Anatomy] Sensory Pathways

April 16, 2016 Anatomy, Neurology No comments , , , , , , , , , , , , , , , , , , ,

The CNS communicates with peripheral body structrues through pathways. These pathways conduct either sensory or motor information; proccessing and integration occur continuously along them. These pathways travel through the white matter of the brainstem and/or spinal cord as they connect various CNS regions with cranial and spinal nerves. A pathway consists of a tract and nucleus. Tracts are groups or bundles of axons that travel together in the CNS. A nucleus is a collection of neuron cell bodies located within the CNS. Nervous system pathways are sensory or motor. Sensory pathways are also called ascending pathways because the sensory information gathered by sensory receptors ascends through the spinal cord to the brain, whereas motor pathways are also called descending pathways because they transmit motor information that descends from the brain through the spinal cord to muscles or glands. Most of the nervous system pathways we discuss in this thread share several general characteristics:

  • Most pathways decussate from one side of the body to the other side at some point in their travels. This decussation means that the left side of the brain processes information from the right side of the body, and vice versa.
  • In most pathways, there is a precise correspondence of receptors in body regions, through axons, to specific functional areas in the cerebral cortex (ascending pathways), and vice versa for descending pathways. This correspondence is called somatotopy.
  • All pathways are composed of paired tracts. A pathway on the left side of the CNS has a matching tract on the right side of the CNS. Because each tract innervates structures on only one side of the body, both left and right tracts are needed to innervate both the left and right sides of the body.
  • Most pathways are composed of a series of two or three neurons that work together. Sensory pathways have primary neurons, secondary neurons, and sometimes tertiary neurons that facilitate the pathway's functioning. In contrast, motor pathways use an upper motor neuron and a lower motor neuron. The cell bodies are located in the nuclei associated with each pathway.

Screen Shot 2016-04-29 at 9.37.43 PMSensory Pathways

Sensory pathways are ascending pathways that conduct information about limb position and the sensations of touch, temperature, pressure, and pain to the brain. Somatosensory pathways process stimuli received from receptors within the skin, muscles, and joints, whereas viscerosensory pathways process stimuli received from the viscera.

Somatosensory Pathways

The multiple types of body sensations detected by the somatosensory system are grouped into three spinal cord pathways, each with a different brain destination: 1.Discriminative touch permits us to describe textures and shapes of unseen objects and includes pressure, touch, and vibration perception; 2.Temperature and pain allow us to detect those sensations, as well as the sensation of an itch; 3.Proprioception allows us to detect the position of joints, stretch in muscles, and tension in tendons. Sensory receptors detect stimuli and then conduct nerve impulses to the central nervous system. Sensory pathway centers within either the spinal cord or the brainstem process and filter the incoming sensory information. These centers determine whether the incoming sensory stimulus should be transmitted to the cerebrum or terminated. Consequently, not all incoming impulses reach the cerebral cortex and our conscious awareness.

Posterior Funiculus – Medial Lemniscal Pathway

Screen Shot 2016-04-30 at 1.49.56 PMThis pathway projects through the spinal cord, brainstem, and diencephalon before terminating within the cerebral cortex. Its name derives from two components: the tracts within the spinal cord, collectively called the posterior funiculus; and the tracts within the brainstem, collectively called the medial lemniscus. This pathway conducts sensory stimuli concerned with proprioceptive information about limb position and discriminative touch, precise pressure, and vibration sensations.

The posterior funiculus – medial lemniscal pathway uses a chain of three neurons to singal the brain about a specific stimulus. Axons of the primary neurons traveling in spinal nerves reach the CNS through the posterior roots of spinal nerves. Upon entering the spinal cord, these axons ascend within a specific posterior funiculus, either the fascinculus cuneatus or the fasciculus gracilis. The fasciculus cuneatus houses axons from sensory neurons originating in the upper limbs, superior trunk, neck, and posterior region of the head, whereas the fasciculus gracilis carries axons from sensory neurons originating in the lower limbs and inferior trunk. The senory input into both posterior funiculi is organized somatotopically – that is, there is a correspondence between a receptor's location in a body part and a particular location in the CNS. Thus, the sensory information originating from inferior regions is medially located within the fasciculus, and the sensory information originating at progressively more superior regions is located more laterally.

Sensory axons ascending within the posterior funiculi synapse on secondary neuron cell bodies housed within a posterior funiculus nucleus in the medulla oblongata. These nuclei are either the nucleus cuneatus or the nucleus gracilis, and they correspond to the fasciculus cuneatus and fasciculus gracilis, respectively. These secondary neurons then project axons to relay the incoming sensory information to the thalamus on the oposite side of the brain through medial lemniscus. Decussation occurs after secondary neuron axons exit their specific nuclei and before they enter the medial lemniscus. As the sensory information travels toward the thalamus, the same classes of sensory input (touch, pressure, and vibration) that have been collected by cranial nerves CN V (trigeminal), CN VII (facial), CN IX (glossopharyngeal), and CN X (vagus) are integrated and incorporated into the ascending pathways, collectively called the trigeminothalamic tract.

The axons of the secondary neurons synapse on cell bodies of the tertiary neurons within the thalamus. Within the thalamus, the ascending sensory information is sorted according to the region of the body involved (somatotopically). Axons from these tertiary neurons conduct sensory information to a specific location of the primary somatosensory cortex.

Anterolateral Pathway

Screen Shot 2016-04-30 at 1.52.32 PMThis pathway is located in the anterior and alteral white funiculi of the spinal cord. It is composed of the anterior spinothalamic tract and the lateral spinothalamic tract. Axons projecting from primary neurons enter the spinal cord and synpase on secondary neurons within the posterior horns. Axons entering these pathways conduct stimuli related to crude touch and pressure as well as pain and temperature. Axons of the secondary neurons in the anterolateral pathway cross over to the opposite side of the spinal cord before ascending toward the brain. This decussation occurs through the anterior white commissure, loacted anterior to the gray commissure. The anterior and lateral spinothalamic pathway, are somatotopically organized: Axons transmitting sensory information from more inferior segments of the body are located lateral to those from more superior segments. Secondary neuron axons synapse on tertiary neurons located within the thalamus. Axons from the tertiary neurons then conduct stimulus information to the appropriate region of the primary somatosensory cortex.

Spinocerebellar Pathway

Screen Shot 2016-04-30 at 1.54.21 PMThe spinocerebellar pathway conducts proprioceptive information to the cerebellum for processing to coordinate body movements. The spinocerebellar pathway is composed of anterior and posterior spino- cerebellar tracts; these are the major routes for transmitting postural input to the cerebellum. Sensory input arriving at the cerebellum through these tracts is critical for regulating posture and balance and for coordinating skilled movements.  ese spinocerebellar tracts are di erent from the other sensory pathways in that they do not use tertiary neurons; rather, they have only primary and second- ary neurons. Information conducted in spinocerebellar pathways is integrated and acted on at a subconscious level.

Anterior spinocerebellar tracts conduct impulses from the inferior regions of the trunk and the lower limbs.  eir axons enter the cerebellum through the superior cerebellar peduncle. Posterior spinocerebellar tracts conduct impulses from the lower limbs, the trunk, and the upper limbs.  eir axons enter the cerebellum through the inferior cerebellar peduncle.


Update on Jul 29 2017

Laminas

A cross section of the gray matter of the spinal cord shows a number of laminas (layers of nerve cells), termed Rexed's laminae after the neuroanatomist who described them. As a general principle, laminae are involved in non-painful was well as painful sensation.

Lamina I – This thin marginal layer contains neurons that respond to noxious stimuli and send axons to the contralateral spinothalamic tract.

Lamina II – Also known as substantia gelatinosa, this lamina is made up of small neurons, some of which respond to noxious stimuli. Substance P, a neuropeptide involved in pathways mediating sensibility to pain, is found in high concentration in laminas I and II.

Lamins III and IV – These are referred to together as the nucleus proprius. Their main input is from fibers that convey position and light touch sense.

Lamina V – This layer contains cells that respond to both noxious and visceral afferent stimuli.

Lamina VI – This deepest layer of the dorsal horn contains neurons that respond to mechanical signals from joints and skin.

Lamina VII – This is a large zone that contains the cells of the dorsal nucleus (Clarke's column) medially as well as a large portion of the ventral grapy column. Clarke's column contains cells that give rise to the posterior spinocerebellar tract. Lamina VII also contains the intermediolateral nucleus (or intermediolateral cell column) in thoracic and upper lumbar regions. Preganglionic sympathetic fibers project from cells in this nucleus, via the ventral roots and white rami communicantes, to sympathetic ganglia.

Laminas VIII and IX – These layers represent motor function neuron groups in the medial and lateral portions of the ventral grapy column. The medial portion (also termed the medial motor neuron column) contains the LMNs that innervate axial musculature. The lateral motor neuron column contains LMNs for the distal muscles of the arm and leg. In general, flexor muscles are innervated by motor neurons located close to the central canal, whereas extensor muscles are innervated by motor neurons located more peripherally.

Lamina X – This represents the small neurons around the central canal or its remnants.


Ascending Fiber System

All afferent axons in the dorsal roots have their cell bodies in the dorsal root ganglia. Different ascending systems decussate at different levels. In general, ascending axons synapse within the spinal cord before decussating.

Dorsal column tract

These tracts, which are part of the medial lemniscal system, convey well-localized sensations of fine touch, vibration, two-point discrimination, and proprioception (position sense) from the skin and joints; they ascend, without crossing, in the dorsal white column of the spinal cord to the lower brain stem. The fasciculus gracilis carries input from the lower half of the body, with fibers that arise from the lowest, most medial segments. The fasciculus cuneatus lies between the fasciculus gracilis and the dorsal gray column; it carries input from the upper half of the body, with fibers from the lower (thoracic) segments more medial than the higher (cervical) ones. Thus, one dorsal column contains fibers from all segments of the ipsilateral half of the body arranged in an orderly somatotopic fashion from medial to lateral.

Ascending fibers in the gracile and cuneate fasciculi terminate on neurons in the gracile and cuneate nuclei (dorsal column nuclei) in the lower medulla. These second-order neurons send their axons, in turn, across the midline via the lemniscal decussation (also called the internal arcuate tract) and the medial lemniscus to the thalamus. From the ventral posterolateral thalamic nuclei, sensory information is relayed upward to the somatosensory cortex.

Spinothalamic tract

Small-diameter sensory axons conveying the sensations of sharp (noxious) pain, temperature, and crudely localized touch course upward, after entering the spinal cord via the dorsal root, for one or two segments at the periphery of the dorsal horn. These short, ascending stretches of incoming fibers that are termed the dorsolateral fasciculus, or Lissauer's tract, then synapse with dorsal column neurons, especially in laminas I, II, and V. After one or more synapses, subsequent fibers cross to the opposite side of the spinal cord and then ascend within the spinothalamic tracts, also called the ventrolateral (or anterior system). These spinothalamic tracts actually consist of two adjacent pathways: The anterior spinothalamic tract carries information about light touch, and the lateral spinothalamic tract conveys pain and  temperautre sensibility upward. 

The spinothalamic tracts, like the dorsal column system, show somatotopic organization. Sensation from sacral parts of the body is carried in lateral parts of the spinothalamic tracts, whereas impulses originating in cervical regions are carried by fibers in medial parts of the spinothalamic racts. Axons of the spinothalamic tracts project rostrally after sending branches to the reticular foramtion in the brain stem and project to the thalamus.

The second-order neurons of both the dorsal column system and spinothalamic tracts decussate. The pattern of decussation is different, however. The axons of second-order neurons of the dorsal column system cross in the lemniscal decussation in the medulla; these second-order sensory axons are called internal arcuate fibers where they cross. In contrast, the axons of second-order neurons in the spinothalamic tracts cross at every segmental level in the spinal cord. This fact aids in determining whether a lesion is in the brain or the spinal cord.

With lesions in the brain stem or higher, deficits of pain perception, touch sensation, and proprioception are all contralateral to the lesion. With spinal cord lesions, however, the deficit in pain perception is contralateral to the lesion, whereas the other deficits are ipsilateral.

Spinocerebellar tract

Two ascending pathways (of lesser importance in human neurology) provide input from the spinal cord to the cerebellum.

Dorsal spinocerebellar tract – Afferent fibers from muscle and skin enter the spinal cord via dorsal roots at levels T1 to L2 and synapse on second-order neurons of the nucleus dorsalis (Clarke's column). Afferent fibers originating in sacral and lower lumbar levels ascend within the spinal cord (within the dorsal columns) to reach the lower portion of the nucleus dorsalis.

The dorsal nucleus of Clarke is not present above C8; it is replaced, for the upper extremity, by a homologous nucleus called the accessory cuneate nucleus. Dorsal root fibers originating at cervical levels synapse with second-order neurons in the accessory cuneate nucleus.

The second-order neurons from the dorsal nucleus of Clarke form the dorsal spinocerebellar tract; second-order neurons from the lateral cuneate nucleus form the cuneocerebellar tract. Both tracts remain on the ipsilateral side of the spinal cord, ascending via the inferior cerebellar peduncle to terminate in the paleocerebellar cortex.

Ventral spinocerebellar tract – This system is involved with movement control. Second-order neurons, located in Rexed's laminae V, VI, and VII in lumbar and sacral segments of the spinal cord, send axons that ascend through the superior cerebellar peduncle to the pale ocerebellar cortex. The axons of the second-order neurons are largely but not entirely crossed.