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.