JD

Sensory and Motor Systems - Comprehensive Notes

Flavor Perception

  • Flavor is derived from a combination of sensory inputs:
    • Taste
    • Olfactory
    • Somatosensory
  • This is an example of multimodal processing.

Miracle Berries (Synsepalum dulcificum)

  • Miraculin, a glycoprotein, binds to taste buds and causes sour things to taste sweet.
  • It tricks the sweet receptors.
  • With miraculin bound, sweet receptor cells depolarize in the presence of H^+.

Sensory Systems Covered

  • Five sensory systems were covered, from receptor to cortex:
    1. Somatosensory
    2. Visual
    3. Auditory
    4. Gustatory
    5. Olfactory
  • In general, each hemisphere receives sensory information from contralateral sides of the body, except for the gustatory system.

General Features of Sensory Systems

  • Transduction: Conversion of sensory stimuli into electrical signals.
  • Coding: Representation of stimulus features by the firing patterns of neurons.
  • Receptive field: The region of sensory space within which a specific stimulus elicits the greatest response from a sensory neuron.
  • Hierarchical Organization: Complex processing of stimuli occurs as information ascends through the system. Mathematically involves pooling information to extract abstract features.
  • Functional Segregation: Cortical areas are functionally specific.
  • Parallel Processing: Multiple pathways process sensory stimuli simultaneously (neural divergence).

Sensation vs. Perception

  • Sensation:
    • Physical process
    • Awareness of stimuli
    • First stage of processing
    • Does not involve organization, combination, or selection of stimuli
  • Perception:
    • Cognitive or psychological process
    • Gives meaning to sensations
    • Second stage of processing
    • Involves organization, combination, and selection to form stimuli into patterns
    • Varies from person to person because the brain interprets stimuli differently based on learning, memory, emotions, and expectations
    • Can occur in the absence of sensation (illusion, hallucination, and cross talk)
  • Bottom-up processing vs. Top-down processing (feedback loops):
    • Neural basis for sensation: Transduction at the sensory receptor & Coding by primary or secondary neurons
    • Neural basis for perception: Engagement of sensory pathways, especially cortical areas

Top-Down Processing Example

  • Expectations lead us to perceive hues differently.

Synesthesia

  • A condition where individuals experience more than one sense simultaneously.
  • Types:
    • Grapheme-color synesthesia: Letters and numbers are associated with specific colors (Read in color).
    • Lexical-gustatory synesthesia: Hearing certain words triggers distinct tastes (Taste Words).
    • Chromesthesia: Certain sounds (like a car honking) can trigger someone to see colors (See sounds).
  • Associated with cross-activation (cross-talk) of brain areas, according to fMRI studies.

Split-Brain Patients

  • Surgically cut corpus callosum.
  • Raises questions about separate or unified consciousness.
  • Can visual information be transferred without the corpus callosum?

Movement

  • Successful interaction with the environment is necessary for survival.
  • Movements range from basic reflexes to complex athletics.
  • Why study movement?

What is Movement?

  • Volitional and Involuntary
  • Conscious and unconscious
  • Examples: Walking, postural adjustments, talking, movements of the arms and fingers.
  • Different specialized motor systems involved.
  • Involves both the CNS and PNS.

Motor Processing

  • "Simple" reflex circuits (involuntary movement):
    • Spinal cord anatomy & neuromuscular junction
    • Muscle contraction and relaxation
    • Muscle fibers, stretch reflex, withdrawal reflex
  • Voluntary movement:
    • Primary motor cortex and other motor cortical areas
    • Basal ganglia: selection of movement
    • Cerebellum: modulation of movement

Motor Hierarchy

  • Premotor/Supplementary motor cortices
  • Subcortical structures: Cerebellum and basal ganglia
  • Primary motor cortex
  • Spinal cord/Reflexes
  • Motor neurons

Features of Motor Systems

  • Relies on hierarchical processing by many structures.
  • Multisensory integration.
  • Feedback.

Spinal Cord Anatomy

  • Dorsal root: Sensory (afferent)
  • Ventral root: Motor (efferent)
  • Key components: Dorsal root ganglion, afferent axon, ventral root, efferent axon, motor neuron, spinal nerve.

Innervation of Skeletal Muscle

  • Alpha motor neurons innervate extrafusal muscle fibers (responsible for muscle's motive force).
  • Alpha motor neuron + muscle fiber(s) = motor unit.
  • Number of muscle fibers in a unit varies depending on the precision of muscle control.

Coordinated Activation of Muscles

  • Necessary for skeletal movement.
  • Muscles can either flex or extend the joint they span.
  • Flexors bring bones closer; extensors increase the distance/angle between bones.
  • Flexors and extensors work in opposition; when one set contracts, the other relaxes.
  • Example: Bending the elbow requires contraction of the biceps (a flexor) and relaxation of the triceps (an extensor).

Neuromuscular Junction (NMJ)

  • The synapse between the terminal buttons of a motor axon and a muscle fiber.

    1. AP reaches terminal button
    2. Voltage-gated Ca^{+2} channels open and Ca^{+2} flows in
    3. Vesicles filled with Ach bind to membrane
    4. Ach binds to nicotinic Ach receptors (nAChRs) on motor endplate
    5. Na^{+} flows in and depolarizes postsynaptic membrane (endplate potential)
    6. AP propagates in muscle fiber
    7. Acetylcholinesterase (AChE) degrades ACh

  • In contrast to postsynaptic potentials in the CNS, an endplate potential ALWAYS causes the muscle fiber to fire.

Patellar Reflex

  • Example of a monosynaptic stretch reflex.
  • Involves:
    • Muscle spindle
    • Extrafusal muscle fibers
    • Dorsal root ganglion
    • Spinal cord (dorsal and ventral roots)
    • Alpha motor neuron

Use of Patellar-Like Reflex

  • Automatic adjustments of muscle positions.
  • Rapid stretch of muscle triggers stretch reflex.
  • Stumble triggers righting reflex.

Polysynaptic Reflex

  • Sensory information can also trigger a polysynaptic reflex.
  • Involves interneurons.
  • Example: Withdrawal reflex from a painful stimulus (hot iron).

Cortical Input and Polysynaptic Reflexes

  • Cortical input can inhibit withdrawal response.
  • Inhibitory signals from the brain can prevent the withdrawal reflex.
  • Simultaneous IPSP and EPSP can cancel each other out.

Motor Processing (Recap)

  • "Simple" reflex circuits (involuntary movement):
    • Spinal cord anatomy & neuromuscular junction
    • Muscle contraction and relaxation
    • Muscle fibers, stretch reflex, withdrawal reflex
  • Voluntary movement:
    • Primary motor cortex and other motor cortical areas
    • Basal ganglia: selection of movement
    • Cerebellum: modulation of movement

Primary Motor Cortex & Other Cortical Motor Areas

  • Supplementary motor area
  • Pre-supplementary motor area
  • Premotor cortex
  • Primary motor cortex
  • Involved in movement of muscles and plans for movements.

Stimulation of Motor Cortex

  • Brief stimulation of motor cortex causes movements of particular contralateral body parts.

Motor Commands

  • Primary motor neurons relay motor commands down descending pathways to alpha motor neurons that stimulate appropriate muscles to contract.
  • Pathways go through basal ganglia, cerebellum, midbrain, pons, medulla, etc., to spinal cord.
  • Support both independent and coordinated limb movement.

Cortical Control of Movement

  • Descending pathways from primary motor cortex go through midbrain, pons, medulla to spinal cord.
  • Facilitate independent and coordinated limb movement.

Primary Motor Neurons

  • Fire 5-100ms before the onset of movement.
  • Encode:
    • The force of a movement.
    • The direction of movement.
    • The extent (distance) of movement.
    • The speed of movement.

Prolonged Stimulation of Motor Cortex

  • Prolonged stimulation (500ms) of regions of motor cortex triggers complex actions.
  • The map of categories was consistent from animal to animal.
  • Stimulation spanned association areas (SMA & premotor) and primary motor cortex.

Organization of Motor Cortex

  • Motor Cortex = primary motor cortex & association areas.
  • Some association areas are involved in planning movements:
    • Posterior association cortices
    • Frontal association cortices
  • Others are involved in initiating movements:
    • (DORSAL) Supplementary motor area (SMA)
    • (VENTRAL) Premotor cortex
  • Information flows hierarchically; activity in association cortices precedes and influences motor cortex.

Association Areas Involved in Planning Movements

  • Parietal cortex receives and integrates:
    • Info about space (what, where) from visual system.
    • Info about spatial location from somatosensory, vestibular, and auditory systems.
  • Posterior association cortices: Parietal cortex, Temporal cortex - involved in organizing auditory and visually guided movements.
  • Frontal association cortices: Prefrontal cortex, Pre-SMA - involved in generating goals and plans for movement based on memories, etc.

Pre-SMA

  • Planning/control of spontaneous movements.
  • Stimulation provokes urge or anticipation of movement.
  • Region is activated just before spontaneous movement.

Association Areas (Recap)

  • Some association areas are involved in planning movements:
    • Posterior association cortices
    • Frontal association cortices
  • Others are involved in initiating movements:
    • (DORSAL) Supplementary motor area (SMA)
    • (VENTRAL) Premotor cortex

Association Areas Involved in Initiating Movements

  1. Supplementary motor area (SMA): learning and performing behavioral sequences.
  2. Premotor cortex: Learning and executing complex movements that are guided by arbitrary sensory info.

SMA (Supplementary Motor Area)

  • Involved in learning and performing sequences of movements.
  • Damage disrupts the ability to perform well-learned sequences of responses.
  • Increased fMRI activity during learned series of button presses.
  • TMS disrupted performance of a series of keys.

Premotor Cortex

  • Involved in learning and executing responses signaled by arbitrary stimuli.
  • Arbitrary info: Info that is not directly related to the movement is signals.
  • Examples: Dance moves prompted by choreographer's request; "wave left hand when you hear the buzz and touch your nose when you hear the bell."
  • Associations between stimuli and movements are arbitrary and must be learned.

Patients with PMC Damage

  • Could not use arbitrary visual, auditory, or tactile cues to make particular movements.
  • They COULD point to correct (1/6) spatial location in which they’d seen a stimuli.
  • They COULD NOT learn to make specific movements in response to arbitrary visual, auditory, or tactile cues.

Association Areas: Planning & Initiating Movements (Recap)

  • PLANNING:
    • Posterior association cortices
    • Frontal association cortices
  • INITIATING MOVEMENT:
    • (DORSAL) Supplementary motor area (SMA)
    • (VENTRAL) Premotor cortex
  • MOTOR CORTEX:
    • Generates movements
    • Communicates with downstream targets
    • Triggers complex actions
  • Information flows hierarchically; activity in association cortices precedes and influence motor cortex.

Primary Motor Neurons (Timing)

  • Fire 5-100ms before the onset of movement.
  • Neural communication (AP propagation & neurochemical signaling across synapses) takes time.
  • The more synapses a signal must travel, the longer it takes.
  • Sensory responses will follow stimuli & motor planning/generation output signals will precede actions.

Prolonged Stimulation of Motor Cortex (Revisited)

  • Prolonged stimulation (500ms) of regions of motor cortex triggers complex actions.
  • The map of categories was consistent from animal to animal.
  • Note: Stimulation spanned association areas (SMA & premotor) and primary motor cortex.

Monosynaptic vs. Polysynaptic Reflexes

  • Monosynaptic: one synapse between sensory and motor neurons; Polysynaptic: more than one synapse between sensory and motor neurons.
  • Monosynaptic stretch reflexes are adjustments (response to sudden change) and postural control (aka righting).
  • Polysynaptic reflexes are ALL OTHER REFLEXES.

Skeletal APs vs. Neuronal APs

  • Yes, for the most part. The steps to generate them are the same, but there are slight difference is timing & shape of AP.

Mirror Neurons

  • Ventral premotor cortex neurons also fire during movements.
  • Mirror neurons in the ventral premotor area (F) respond when monkey performed or saw movement.
  • Mirror neuron firing contains representation of complex motor behavior.
  • Continues to process sensory and cognitive information after movement is initiated.

Location of Mirror Neurons

  • Ventral premotor cortex & inferior parietal lobule.

Function of Mirror Neurons

  • Imitating and comprehending movements.
  • Understanding intentions.
  • Encode action and intent of action.
  • Thought to support empathy.

Supplementary Motor Area (SMA) Damage

  • Damage resulted in monkeys being unable to perform a once-familiar response, specifically pushing in a lever and then turning it to the left.
  • This result suggests that this brain area is involved in executing well-learned sequences of motor responses.

Subcortical Structures & Movement Disorders

  • Basal ganglia
  • Cerebellum
  • Reticular formation

Motor Processing (Again)

  • "Simple" reflex circuits (involuntary movement):
    • Spinal cord anatomy & neuromuscular junction
    • Muscle contraction and relaxation
    • Muscle fibers, stretch reflex, withdrawal reflex
  • Voluntary movement:
    • Primary motor cortex and other motor cortical areas
    • Basal ganglia: selection of movement
    • Cerebellum: modulation of movement

Motor Hierarchy (Revisited)

  • Premotor/Supplementary motor cortices
  • Subcortical structures: Cerebellum and basal ganglia
  • Primary motor cortex
  • Spinal cord/Reflexes
  • Motor neurons

Sensory-Motor Organization

  • Basal Ganglia: Motivation, Planning, Programming, Integration, Execution
  • Cerebellum: Muscles
  • Motor cortex
  • Spinal Column
  • Brainstem
  • Pre-motor areas
  • Limbic & Recticular areas
  • Sensory systems

Brain Areas

  • Motor cortex: Primary motor cortex & association areas
  • Cerebellum
  • Basal Ganglia

Sub-Cortical Loops

  • Basal ganglia
  • Cerebellum

Basal Ganglia

  • A series of interconnected subcortical nuclei involved in movement.
  • Diseases of the BG à movement disorders (e.g., Parkinson, Huntington, Tourette's, Tics).

Dopamine

  • Released from cells in the Midbrain (mesencephalon) Tegmentum.

    • Periaqueductal gray (PAG): pain modulation/analgesia
    • Substantia Nigra & Ventral Tegmental Area (VTA): DA cell bodies

  • Dopamine cells send projections to many areas of the brain, including the striatum.

  • This means they release DA from varicosities and terminal buttons in many brain areas.

Cells in the Striatum

  • 95% are Medium Spiny Neurons (MSNs), also called Spiny Projection Neurons (SPNs).
    • They release GABA.
    • Can be subdivided based on dopamine receptor they express (D1R neurons, D2R neurons).
  • 5% are interneurons either releasing Achetlycholine (ACh) or GABA.

Dopamine Receptors

  • Dopamine binds to two metabotropic receptors with different g-proteins:
    • D1 receptors: Increases the excitability of cells
    • D2 receptors: Decreases the excitability of cells

Dopamine as Neuromodulator

  • Dopamine is a neuromodulator that binds to two metabotropic receptors with different g- proteins
  • Glutamate receptor: depolarizes the cells
  • D1 receptors: Increases the excitability of cells
  • D2 receptors: Decreases the excitability of cells
  • Cortex DA
    • Supports Cortical excitation
  • Cortex DA
    • Blocks Cortical excitation

Normal Basal Ganglia Circuit

  • Two pathways connect cortex to striatum:
    1. Direct pathway (D1R neurons)
    2. Indirect pathway (D2R neurons)

Pathways Through the Basal Ganglia

  1. Direct pathway: D1 cells à output nuclei (GPi)à à excitation of thalamus à excitation of cortex
  2. Indirect pathway: D2 cells à via GPe /STN to output nuclei (GPi)à à inhibition of thalamus/cortex & no excitation of the cortex

Normal Basal Ganglia Circuit (with DA)

  • Under normal conditions:
    • DA release activates D1R neurons & inhibit D2R neurons
    • Activates the direct pathway & inhibits the indirect pathway

Basal Ganglia Interaction

  • Interacts with many motor-associated cortical areas.
  • Excited by direct pathway; inhibited by the indirect pathway.

Hyper- and Hypo- Kinetic Circuits

  • Hyperkinetic movements result from direct > indirect (Huntington’s).
  • Hypokinetic movements result from indirect > direct (Parkinson’s).
  • Balance between the two is key!

Huntington’s Disease

  • Degeneration of caudate and putamen, particularly GABAergic and ACh-ergic neurons via apoptosis due to abnormal huntingtin (htt) gene.
  • Progressive chorea (jerky, random, uncontrollable movements).
  • No current treatment but possible treatment with small interfering RNA (siRNA) to interrupt transcription of htt gene.

Parkinson’s Disease

  • Hypokinetic circuit.
  • 2nd most common neurodegenerative condition (Alzheimer’s is most common).
  • Tremor, rigidity, mask-like facial expression.
  • Bradykinesia (slow movement and loss of spontaneous movement).

Parkinson's Pathology

  • Diminished substantia nigra
  • Decrease in dopaminergic projection to the striatum

Parkinson’s Disease BG

  1. Loss of Dopamine = decreased direct pathway activity & Increased indirect pathway activity (Hypokinetic state).
  2. Inhibition of Thalamus and Cortex.

Treatment Options for PD

  • L-Dopa to “top up” dopamine levels and hopefully restore normal modulation of basal ganglia; unwanted side effects and not a long-term solution.
  • Stereotactic surgery: selective lesions (pallidotomy, STN) and/or deep brain stimulation to try and restore the balance in the pathways.