Notes

Sensory Receptors

Sensory Receptors

• Vision, Smell, Taste, Touch, Thermal Senses, Pain, Hearing, Balance, Proprioception.
• The Somatosensory encapsulated receptors are 4:
  • Meissner Corpuscle
  • Merkel-Neurite Complex
  • Ruffini Corpuscle
  • Pacinian Corpuscle

Some of these receptors quickly adapt, while others don't. Fibers are classified as either:

• Rapidly Adapting (RAs)
• Slowly Adapting (SAs)
• Also in terms of the size of their Receptive Field (The size of the area on the skin from which they can be activated) (it is also related to the position of the receptor, indeed superficial receptors tend to have smaller RF than deeper ones).

RAs respond only at the beginning and end of sustained displacements (i.e., to transients) but respond well to higher frequency vibrations. Two types:

• RA I: Meissner Corpuscles (10 - 200 Hz) (small RF)
• RA II (PC): Pacinian Corpuscles (70 - 1000 Hz) (large RF)

SAs respond throughout sustained displacements of the skin, and are thus suited to coding the duration and magnitude of mechanical stimuli. Two types:

• SA I: Merkel Receptors/Disks (small RF)
• SA II: Ruffini Endings (large RF).

Brain Motor Circuitry, Pathways & Processing

Spinal Cord Circuitry Motor Unit 1

• Small diameter motor neuron.
• High input resistance.
• Needs small drive from spinal interneuron (and thus M1) to drive an AP in the postsynaptic neuron. Motor Unit 2
• Large diameter motor neuron.
• Low input resistance.
• Needs large drive from spinal interneuron (and thus M1) to drive an AP in the postsynaptic neuron.

Gray Matter Gray matter can be found in the inner part of the spinal cord. It presents a localized representation of the different limbs in the spinal cord.

White Matter It presents two different pathways:

• Motor and Descending (efferent) Pathways
  • Pyramidal Tracts
  • Extrapyramidal Tracts
• Sensory and Ascending (afferent) Pathways
  • Dorsal Column Medial Lemniscus System
  • Spinocerebellar Tracts
  • Anterolateral System

Spinal Cord Reflex ARC For reflexes, there is a loop directly within the spinal cord (does not go all the way up to the CNS). The dorsal root of the spinal cord receives sensory signals from Golgi tendons (muscle stretch sensor) and directly projects to the ventral root, which through gamma and alpha motoneurons induce muscle movements.

Central Pattern Generator (CPG) This is some kind of circuitry between the right and left side of the spinal cord which induces the ability to do some movements that involve both sides of the body (e.g., walking or swimming). Flexing and extending muscles alternatively on both sides through excitation and inhibition via interneurons.

Dermatomes Dermatomes are areas of skin that connect to a specific nerve root of the spine. There are 31 pairs of spinal nerves, forming nerve roots that branch from the spinal cord. Spinal nerves are named and grouped by the region of the spine that they are associated with (cervical nerves, thoracic nerves, lumbar nerves, sacral nerves, coccygeal nerves). There is some redundancy transmitted to the dorsal root of the spinal cord. There is essentially some re-bundling of skin nerves together and they are overlapping. Nerve fibers of the skin are rebundled and mixed together and sent to spinal cord. Because if one of the dorsal roots is damaged (accident/tumor), then you have redundancy, which allow to avoid losing all the sensation in that area.

Modality Segregation It is the basic principle of organization of the somatosensory system. Information from each class of receptors reaches a different group of neurons in the CNS and these neurons project to higher levels along segregated "parallel" pathways. This segregation begins with the place of termination of different classes of afferent axon in the spinal cord. It continues with two major ascending pathways:

• The Dorsal Column - Medial Lemniscal Pathway (Touch information).
• The Spino - Thalamic Pathway (Pain & Temperature information).

The Dorsal Column - Medial Lemniscal Pathway

• The ascending branches of Aβ axons (conveying discriminative touch information, i.e., carrying mechanoreceptive information) ascend in the dorsal columns (the gracile and cuneate fasciculi), and synapse on cells in the dorsal column nuclei (DCN) in the medulla (the gracile and cuneate nuclei, respectively).
• The axons of DCN cells cross the midline and ascend in the medial lemniscus to the lateral division of the ventro-posterior nucleus (VPL) of the thalamus.
• VPL cells in turn project to the primary somatosensory cortex (SI).

Things to Note About Dorsal Column - Medial Lemniscal Pathway

• The Gracile Fasciculus extends the entire length of the spinal cord; it and the Gracile Nucleus contain a representation of the feet, legs, and lower trunk.
• The Cuneate Fasciculus begins at the cervical level; it and the Cuneate Nucleus contain a representation of the hands, arms, and upper trunk.
• The entire system is topographically organized (i.e., adjacent parts of the body surface are represented by adjacent neurons - Somatotopy).
• The decussation (crossing over) of the medial lemnisci results in a representation of the contralateral body surface on each side of the brain at levels above the DCN.

The Spino - Thalamic Pathway

• It represents the second-major pathway.
• Small-diameter myelinated and unmyelinated axons (Aδ (first pain) and C (second pain) fibers serving temperature sensitivity and nociception) terminate in the spinal cord itself.
• The axons of the spinal neurons then cross the midline and ascend as the anterolateral system.
• Most of these fibers (constituting the spino-thalamic system) terminate in VPL and in the intralaminar and posterior groups of thalamic nuclei.
• Other ascending fibers terminate in the reticular formation (thespino-reticular system) and in the midbrain.
• The VPL neurons receiving spino-thalamic input are segregated from those receiving medial lemniscal input and project to both primary and secondary somatosensory cortex (SI and SII).

The Trigeminal System

• It is dedicated to the brain and the neck. Conveys somatosensory input from the face.
• Large-diameter myelinated axons of the trigeminal ganglion conveying discriminative touch information terminate in the principal trigeminal nucleus.
• The axons of these cells then cross the midline, join the medial lemniscus, and terminate in the medial division of the Ventro-Posterior Nucleus (VPM).
• Small diameter lightly-myelinated and unmyelinated axons of the trigeminal ganglion conveying thermal and nociceptor information descend in the spinal trigeminal tract and terminate in the spinal trigeminal nucleus.
• The axons of these cells then project to VPM and to the posterior and intralaminar thalamic nuclei (i.e., rather like the anterolateral system).
• Hence, we have a separation again of mechanoreceptors from thermoreceptors.

The Somatosensory Thalamus

• The ventrobasal complex of the thalamus has the two major divisions previously described:
  • VPL (somatosensory information from the body)
  • VPM (somatosensory information from the face)
• Both are somatotopically organized.
• Thalamic neurons have adaption properties (SA vs RA) like those of peripheral neurons, but the RFs are larger than those of dorsal root ganglion cells and are commonly concentric, with a central excitatory area and a surrounding inhibitory area.

Thalamo-Cortical circuit It is a neural pathway that connects the thalamus, a relay station in the brain, with the cortex. In this circuit, sensory information from the body is transmitted to the thalamus, which processes and filters the information and then sends it to the relevant regions of the cortex for further processing. The cortex, in turn, sends feedback to the thalamus to regulate the flow of incoming information. This loop allows for the integration of sensory information and the generation of conscious perception and action.

Cortical Association Areas These areas represent the high-level processing in the cortex, which take care of communicating between sensory cortex processing and motor processing. The corpus callosum connects the two brain hemispheres integrating both parts of the body. The association areas can be found in the posterior parietal cortex, anterior parietal cortex, temporal association cortex etc... A major role in the process of integrating multisensory information is played by interneurons.

Motor System Corticospinal Pathway

• Origins: Primary Motor Cortex (MI), Premotor Cortex, Supplemental Motor Cortex, Anterior Paracentral Gyrus, Parietal Lobe (including SI) and Cingulate Gyrus.
• Collaterals: Small percentage of Corticospinal Neurons
  • 1. Midbrain (primarily red nucleus)
  • 2. Trigeminal Nuclei
  • 3. Pontine Nuclei
• Termination is Spinal Cord: mostly laminae 3-7, few in ventral horn and laminae 1-2; mostly innervating interneurons, although some innervation of alpha motor neurons.
• If you measure from a muscle with an EMG and pyramidal neuron in the cortex - we find correlation between spikes and that the muscles are directly controlled from the cortex.

A Hierarchy of Motor Areas

Representation of Movements in M1 Single unit activity upon arm movements in different directions. There exist some kind of population vector representation of neurons in M1. If we have to move an arm in a specific direction, we have specific neurons that fire a lot and others that do not fire at all. In general, all neurons have some preferred direction and certain strength to a specific angle. This means that, for example, a neuron will fire maximally for movement of right arm at 90 degrees, and decreases gradually in response for 80/100 degrees, 70/110 degrees, and so on.

Inputs to the Basal Ganglia Basal ganglia receives widespread input from cortical areas. It integrates inputs from motor and sensory areas. It presents some topographic organization and shows both divergence and convergence. In the case of divergence, information from many neurons in the cortex projects to a smaller number of neurons in the basal ganglia, allowing for integration and processing of information from many sources. In the case of convergence, information from a single neuron in the basal ganglia projects to many neurons in the thalamus and cortex, distributing the processed information to multiple targets. This processing of information by the basal ganglia contributes to the regulation of movement and the selection of appropriate motor response.

The cortico-basal ganglia-thalamic network refers to a group of interconnected brain regions that play a critical role in motor control, attention and decision-making. The network consists of the cortex, the basal ganglia (group of subcortical nuclei including caudate-putamen and globus pallidus) and the thalamus. In this network, the information flows from the cortex to the basal ganglia, where it is processed and integrated with other information. The processed information then flows to the thalamus, which distributes it to different areas of the cortex.

Basal Ganglia Loops and Non-Motor Brain Functions

Organization of the Cerebellum

• Vestibulocerebellum: Evolutionary oldest, inputs from vestibular organ, affects balance and eye movements, if lesioned vomiting and spontaneous eye movements.
• Spinocerebellum - Vermis: Cooperates with vestibulocerebellum, it receives inputs from spinal cord, coordinates posture and locomotion via the deep cerebral nucleus fastigii and the formation reticularis, it is involved in the rough control of limb movements.
• Spinocerebellum - Intermediate Hemisphere: It receives inputs from spinal cord, it is involved in the fine control of distal members like fingers, it provides sensory information from extremities, it controls dorsolaterally descending pathways (rubrospinal, corticospinal).
• Cerebrocerebellum: it is receives inputs from cerebral cortex via pontine nuclei, it projects to motor and premotor cortical areas.

Motor Coordination by Cerebellum and Basal Ganglia

The cerebellum and basal ganglia play complementary roles in motor coordination and are intricately interconnected. The cerebellum is involved in fine-tuning of movements, ensuring that they are accurate, smooth and coordinated. It does this by receiving sensory information about limb position and movement using that information to adjust motor output from the cortex. The cerebellum also helps to learn and store motor skills and habits, allowing for automatic and efficient movements. The basal ganglia are involved in the selection and initiation of movements. They receive input from the cortex and other brain regions, process that information, and then output signals that either facilitate or inhibit movement. The basal ganglia plays a critical role in controlling voluntary movement. The relationship between the cerebellum and basal ganglia can be thought of as a feedback loop. The basal ganglia select and initiate movements, while the cerebellum fine-tunes and modulates those movements based on sensory information. This interaction allows for smooth and coordinated execution of movements.

Formatio Reticularis (Reticular Formation) It is a complex network of nerve cells that is found throughout the brainstem and is involved (among many functions) in the control of movements and maintaining posture by integrating sensory information about the body's position in space.

Descending Brainstem Pathways

• Ventromedial System
  • Vestibulospinal tract: it originates in the vestibular nuclei of the brainstem and is involved in the regulation of balance and posture.
  • Reticulospinal (mainly mensencephalic and pontine part): it originates in the reticular formation of the brainstem and is involved in the regulation of autonomic functions, such as blood pressure, respiration and reflexes.
  • Mostly bilateral
  • Control of erect posture
  • Coordination of body movements (arms and legs)
• Dorsolateral System
  • Rubrospinal tract: it originates in the red nucleus of the brainstem and is involved in the regulation of movement and the modulation of spinal reflexes.
  • Reticulospinal (mainly medullary part): it originates in the reticular formation of the brainstem and is involved in the regulation of autonomic functions, such as blood pressure, respiration and reflexes.
  • Activate flexors, inhibit extensors
  • Cooperate with corticospinal tract
  • Facilitate flexion-based movements
  • Support fine motor control
• Monoaminergic System
  • Noradrenergic
  • Serotoninergic
  • Relevant for locomotion control

Connectivity of Descending Pathways

• Further support function of the medial and lateral pathways.
• Medial interneurons innervate multiple spinal cord segments and project bilaterally.
• Lateral interneurons are confined to few segments and remain unilateral.