Free Response: EXAM II

What comprises the “motor unit”, and how does this relate to the control of muscle force generation (i.e. what is the size principle)?

1. A motor unit consists of a single alpha motor neuron and all the muscle fibers it innervates. Small motor units innervate few muscle fibers and generate less forces, while large motor units innervate many fibers and generate more force. 

2. According to the size principle, small motor neurons are recruited first because they have higher input resistance and reach threshold with less synaptic input. As force demands increase, progressively larger motor units are recruited. This allows fine motor control, smooth force production, and greater resistance to fatigue.

1.  What are Pacemaker neurons? What makes them fire action potentials? How might two or more different pacemaker cells be connected to create a central pattern generator circuit?

1. Pacemaker neurons are neurons that fire rhythmic bursts of action potentials spontaneously without requiring synaptic input. 

2. They fire because depolarizing leak currents (such as persistent sodium currents) slowly bring the membrane potential to threshold. The frequency of firing depends on the size of the leak current and can be modified by neurotransmitters and hormones.

3. Multiple pacemaker neurons can be linked through reciprocal inhibitory interneurons, causing them to fire out of phase with one another. This arrangement forms a central pattern generator (CPG) that produces rhythmic behaviors such as walking, breathing, swimming, and chewing.

1. What is the functional difference between proprioceptive feedback from muscle spindles and Golgi tendon organs? Where and how is this sensory feedback integrated into descending motor commands?

1. Muscle spindles detect changes in muscle length and stretch, while golgi tendon organs (GTOs) detect muscle tension and force. Muscle spindle feedback travels through Ia and II afferents and excites alpha motor neurons to resist stretch (myotatic reflex). GTO feedback travels through Ib afferents and activates inhibitory interneurons that reduce excessive muscle force (inverse myotatic reflex). This proprioceptive information is integrated within the spinal cord circuits, local interneurons, central pattern generators, the cerebellum,, and descending motor pathways to continuously adjust ongoing movements.

1. What is the most important anatomical and functional distinction between the corticospinal and corticobulbar (upper) motor pathways? Which one evolved first?

1. The corticospinal tract projects from the motor cortex directly to spinal motor neurons and is specialized for precise, fractionated control of distal muscles, especially the hands and fingers. The corticobulbar tract projects from the cortex to brainstem motor centers and central pattern generators that control more stereotyped behaviors such as chewing, swallowing, breathing, and other cranial motor functions. Evolutionarily, the corticobulbar system evolved first, while the corticospinal pathway expanded later in primates to support fine motor skills and tool use.

1. What is the “receptive field” of a Betz cell in the primary motor cortex?

1. The receptive field of a Betz cell (or other M1 neuron) is the specific sensory input, muscle stretch, joint position, or cutaneous stimulus that influences its firing. In the primary motor cortex, neurons have both a sensory receptive field and a motor field that are functionally linked. This allows the neuron to generate movement while simultaneously monitoring sensory feedback resulting from that movement. Betz cells are large pyramidal neurons located in layer V of the primary motor cortex and project through the corticospinal tract

1. The somatotopic map of the primary motor cortex is very imprecise, partly because it appears to encode the coordinated activation of many functionally related muscle groups to perform useful actions. This coordination is hypothesized to arise from “neural population vectors”. Give an example of what this means and how neural population vectors can be measured?

1. Individual motor cortical neurons are broadly tuned and have a preferred movement direction, but no single neuron specifies movement precisely. Instead, movement direction is represented by the combined activity of many neurons called a population vector. For example, reaching northeast results from the weighted average of many neurons firing at different rates, each preferring different directions. Population vectors are measured by recording simultaneously from groups of motor cortex neurons and calculating the vector sum of their firing rates and preferred directions. The direction of the resulting vector predicts the intended movement

1. Diagram the basic circuit of the cerebellar cortex, showing (and labeling) a Purkinje cell, granule cell, parallel fiber, mossy fiber, climbing fiber, and their connection to the deep cerebellar nuclei. What do the inputs and outputs of the cerebellar cortex represent regarding the hypothesized function of the cerebellum?

1. Mossy Fibers ↓ Granule Cells ↓ Parallel Fibers ↓ Purkinje Cell ↓ (inhibitory) Deep Cerebellar Nuclei ↓ Motor Cortex/Brainstem Climbing Fibers ↓ Purkinje Cell

2. The cerebellum receives two major inputs:

   1. Mossy fibers carry sensory and proprioceptive feedback representing actual movement.

   2. Climbing fibers carry copies of descending motor commands representing intended movements.

3. Purkinje cells compare these signals and generate an inhibitory output to the deep cerebellar nuclei. The deep nuclei then send corrective excitatory signals to motor pathways. The cerebellum is therefore thought to function as a comparator, detecting movement errors and generating corrective signals that smooth and coordinate movement.

1. What are the most significant inputs and outputs of the striatum and how do they relate to the hypothesized general function of the basal ganglia? What is the functional distinction between the “direct” and “indirect” pathways through the BG?

1. The striatum receives:

   1. Excitatory glutamatergic input from the cerebral cortex

   2. Dopaminergic input from the substantia nigra pars compacta

2. The basal ganglia output travels through the globus pallidus and substantia nigra to the thalamus, which projects back to the cortex.

3. The direct pathway disinhibits the thalamus and facilitates desired movements ("gas pedal").

4. The indirect pathway increases thalamic inhibition and suppresses competing or unwanted movements ("brake").

5. Together they help select appropriate actions while suppressing competing motor programs.

1. Describe the physiological basis of Parkinson’s disease and explain what this reveals about how the basal ganglia contribute to the control of movement. How does this inform current treatments and therapies for Parkinson’s patients?

1. Parkinson's disease results from degeneration of dopamine-producing neurons in the substantia nigra pars compacta. Reduced dopamine weakens the direct pathway and strengthens the indirect pathway, causing excessive inhibition of the thalamus and difficulty initiating movement (bradykinesia). This demonstrates that the basal ganglia normally facilitate desired movements and suppress unwanted ones through balanced direct and indirect pathway activity.

2. Common treatments include:

   1. Levodopa (L-DOPA) to restore dopamine levels

   2. Dopamine agonists

   3. Deep brain stimulation (DBS) when medications lose effectiveness

   4. These treatments aim to restore activity balance within basal ganglia circuits

1. What are mirror neurons? Why are they called that, and where were they first found? What types of behaviors are they hypothesized to serve? 

1. Mirror neurons are neurons that fire both when an individual performs an action and when they observe someone else performing the same action. They are called "mirror" neurons because they appear to mirror the observed behavior in the observer's brain. They were first discovered in the ventral premotor cortex (area F5) of monkeys. They are hypothesized to contribute to observational learning, imitation, action understanding, social cognition, empathy, and language development