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Motor System Overview

  • Introduction to Motor System

    • Focus areas:

    • Muscles

    • Motor neurons

    • Movement autopilot

    • Cortical motor planning

Muscles

  • Fundamental Molecular Mechanisms

    • Mechanism: How do neural signals convert into physical force?

  • Motor Neurons

    • Problem: How does a motor neuron rapidly and synchronously trigger muscle contraction?

  • Movement Autopilot

    • Question: How does the central nervous system create coordinated, rhythmic patterns necessary for automatic actions like breathing?

  • Cortex and Complex Movement

    • Analogy: The conductor and the orchestra.

    • Inquiry: How does the cortex encode voluntary actions and plan complex movements without premature execution?

Muscle Fiber Structure

  • Muscle Fiber Definition

    • Description: A single elongated cell specialized for contraction.

  • Myofibrils

    • Definition: Cylindrical protein structures containing repeating units called sarcomeres.

    • Composition: A single muscle fiber contains multiple myofibrils (thick and thin filaments).

Sarcomere Structure

  • Definition of Sarcomere

    • Smallest functional unit of muscle contraction.

    • Components: Overlapping thick (myosin) and thin (F-actin) filaments arranged orderly.

  • Molecular Basis of Contraction: Actin and Myosin Dynamics

    • Sliding Filament Model:

    • Myosin (thick) and F-actin (thin) filaments slide past each other.

    • Myosin's power stroke generates mechanical force.

    • Power stroke results from the pivoting of the myosin head, pulling actin towards the sarcomere center.

Myosin Functionality

  • Myosin Description

    • Myosin is an F-actin binding motor protein.

    • Structure includes a long tail and a globular head facilitating cross-bridging between thick and thin filaments.

  • Power Stroke Mechanism

    • Sequence of events during muscle contraction:

    1. Myosin head pivots (power stroke), pulling actin.

    2. Myosin is classified as an ATPase, possessing an ATPase domain in its head that hydrolyzes ATP into ADP.

    3. ATP binding to myosin leads to the dissociation of myosin from actin.

    4. Hydrolysis of ATP causes conformational change in the myosin head.

    5. The ADP-myosin complex rebinds to actin.

    6. Release of ADP and inorganic phosphate induces the power stroke.

Excitation-Contraction Coupling (ECC)

  • Definition

    • Excitation-Contraction Coupling (ECC) links motor neuron activity to muscle contraction via calcium ion regulation.

  • Mechanism of ECC

    • Steps in muscle contraction:

    1. Synaptic transmission occurs between the motor neuron axon terminal and the muscle fiber.

    2. Action potentials in motor neurons lead to calcium ion (Ca²⁺) release in muscle fibers.

    3. Muscle depolarization propagates through T-tubules, which are networks of tunnels in muscle fibers.

    4. Resulting depolarization triggers Ca²⁺ release from the sarcoplasmic reticulum (SR), initiating rapid and synchronous contraction of sarcomeres.

Sequence of Events for Muscle Contraction

  • Order of Events

    • A. ATP hydrolysis

    • B. Release of Ca²⁺ from sarcoplasmic reticulum

    • C. Action potential in the motor neuron

    • D. Power stroke occurs

    • E. Activation of the nicotinic acetylcholine receptor

    • F. ADP-myosin binds to actin

    • G. Release of acetylcholine

    • H. Flow of K⁺ and Na⁺ ions through their receptors

    • I. Movement of troponin/tropomyosin

  • Correct Sequence: C, G, E, H, B, I, F, D

    • Ca²⁺ induces a conformational change in actin, allowing both thin and thick filaments to interact, resulting in myosin power strokes.

Coordination of Muscle Activation

  • Activation of Different Muscles

    • Mechanism: Coordination through the alternating contraction of extensor and flexor muscles as antagonistic pairs around joints.

  • Rhythmic movements

    • Requirement: Coordinated and rhythmic contraction patterns, essential for actions like breathing.

Central Pattern Generators (CPGs)

  • Definition & Role

    • Central pattern generators are networks of neurons in the central nervous system capable of producing rhythmic output for coordinated muscle contractions without sensory feedback.

  • Diaphragm Function

    • In respiration, the diaphragm contracts and relaxes as the primary muscle for breathing.

Rhythm Generators vs. Pattern Generators

  • Rhythm Generators

    • Function: Set the beat (inspiration-expiration timing).

    • Characteristics: Neurons exhibit intrinsic bursting or pacemaker properties and produce oscillations.

  • Pattern Generators

    • Function: Shape the output patterns to motor neurons, dictating how muscles move.

    • Features: Networks of interneurons or motor neurons organizing activation across different muscle groups.

Neuronal Dynamics in CPGs

  • Example: Crustacean Stomatogastric Ganglion

    • Neurons in this ganglion serve as model systems for identifying central pattern generators, specifically the AB interneuron identified as pacemaker cells.

  • Pacemaker Cell Characteristics

    • Produce rhythmic output even in absence of input, allowing for self-driven rhythmic activity.

    • Experimental setups include intracellular recording from isolated neurons which demonstrate rhythmic firing independent of synaptic inputs.

Membrane Potentials in Pacemaker Cells

  • Resting Membrane Potential

    • Unstable in pacemaker cells, exhibiting depolarization, repolarization, and hyperpolarization phases.

  • Role of Ion Channels

    • TTX (Tetrodotoxin) can block action potential firing but does not inhibit rhythmic membrane potential changes, indicating voltage-gated Na⁺ channels are unnecessary for this action.

    • The rhythmic potential changes are significantly the result of interactions among low-threshold voltage-gated Ca²⁺ channels, voltage-gated K⁺ channels, and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.

CPG Structure and Output

  • Connection Patterns in CPGs

    • Certain connection patterns contribute to rhythmic output within oscillatory circuits.

  • Example

    • The overlap of AB interneurons with motor neurons collectively contribute to rhythm generation within the CPG.

Breathing Cycle and CPGs

  • Identification of the CPG for Inspiration

    • Pre-Bötzinger complex (pre-BotC) serves a critical role in generating respiratory rhythm.

  • Neuronal Activity During Breathing

    • Rhythmically active neurons in the CPG are responsible for regulation and execution of the breathing cycle consisting of three phases:

    1. Inspiratory phase

    2. Expiratory phase

    3. Post-inspiratory phase

  • Role of the Pre-Bötzinger complex

    • Essential for orchestrating breathing patterns and maintaining necessary cycles of inspiration and expiration.

  • Implications of Disruption

    • Lesioning experiments demonstrate that removal of the pre-Bötzinger complex diminishes rhythmic motor output, signalling the importance of this region in sustaining respiratory patterns.

CPG Molecular and Developmental Basis

  • Molecular Foundation

    • A subset of Dbx1+ progenitor-derived neurons in the pre-BotC plays a vital role in generating rhythmic patterns for breathing.

  • Experimental Observation:

    • Neurons tagged for photostimulation during expiration phases indicate their necessity for rhythm generation.

  • Effects of Photostimulation Timing

    • Timing of photostimulation influences respiratory output, highlighting the sophisticated interaction required for rhythmic breathing.

  • Breathing Center Circuitry

    • Comprised of three interacting oscillator circuits situated in the medulla (brainstem), important for sustaining the rhythmic breathing cycle.