Nervous System Functions, Cellular Organization, and Microenvironment

Introduction to the Nervous System and Human Physiology II

The nervous system is a complex network responsible for coordinating and regulating body activities. Its primary roles include:

• Sensation and Perception: Processing sensory information from the environment and the body.

• Motor Control: Governing voluntary and reflex movements.

• Cognition: Managing higher-order functions such as thought, learning, and memory.

• Emotions: Regulating psychological states and feelings.

• Sleep: Coordinating the circadian rhythms and sleep-wake cycles.

Functional Framework

The nervous system operates through a continuous loop of information processing:

1. Sensory Input: Receiving data from the external or internal environment.

2. Cognitive State: Processing and integrating input based on the current internal state.

3. Motor Output: Executing responses, which may be voluntary or reflex-based.

Cellular Components of Nervous Tissue

Nervous tissue consists of two primary categories of cells: Neurons and Glia.

Neurons

Neurons are the fundamental signaling units. Their structure includes:

• Cell Body (Soma): Contains the nucleus and metabolic machinery.

• Dendrites (Apical and Basal): Receive incoming signals.

• Axon Hillock: The trigger zone where the action potential is initiated.

• Axon: The initial segment and the conductive portion of the neuron.

• Myelin Sheath: Insulation provided by glial cells (Oligodendrocytes in CNS, Schwann cells in PNS).

• Nodes of Ranvier: Gaps in the myelin sheath for signal regeneration.

• Presynaptic Terminals: Release neurotransmitters into the synapse to communicate with postsynaptic cells.

Glial Cells (The 'Glue')

Glial cells provide support, protection, and regulation. They are divided by system:

Central Nervous System (CNS) Glia

• Astrocytes (Star-shaped):

  • Take up excess $K^+$ ions, water, and neurotransmitters from the extracellular space.

  • Help form the blood-brain barrier (BBB).

  • Provide substrates for ATP production.

  • Secrete neurotrophic factors.

• Oligodendrocytes: Generate myelin sheaths for multiple axon segments in the CNS.

• Microglia: Modified immune cells that act as scavengers, removing debris and pathogens.

• Ependymal Cells: Create selective barriers between compartments and serve as a source of neural stem cells.

• Glial Stem Cells: Precursors that can differentiate into new neurons or glial cells.

Peripheral Nervous System (PNS) Glia

• Schwann Cells: Form myelin sheaths for single axon segments in the PNS and secrete neurotrophic factors.

• Satellite Cells: Support neuronal cell bodies within ganglia.

Neuronal Networks and Circuits

Every nerve cell is integrated into a circuit that mediates specific behaviors, such as the quadriceps (extensor) and hamstring (flexor) reflex.

Circuit Principles

• Divergence: A single input neuron reaches different points or multiple target neurons, increasing the response footprint.

• Convergence: Multiple inputs integrate into a single neuron, allowing for the integration of different types of information.

Inhibitory Regimes

1. Feedback Inhibition: An afferent neuron excites a motor neuron, which in turn excites an inhibitory interneuron that acts back upon the same or related neurons to limit the strength of the response.

2. Feedforward Inhibition: An afferent neuron innervating a specific muscle (e.g., extensor) excites its corresponding motor neuron while simultaneously exciting an inhibitory interneuron that inhibits the antagonist motor neuron (e.g., flexor).

Functional Regions and Electrical Signaling

Neurons can be categorized into four functional regions regardless of their specific type (Sensory, Motor, Interneuron, Neuroendocrine):

1. Input Region: Receives signals (graded receptor or synaptic potentials).

2. Integrative Region: Located at the trigger zone; determines if the threshold for an action potential is met.

3. Conductive Region: The axon, where the action potential travels as an all-or-nothing signal.

4. Output Region: The synaptic terminal where neurotransmitters are released.

Potential Types

• Receptor Potentials: Graded potentials resulting from sensory stimuli (e.g., muscle spindle stretch). Their amplitude and duration are proportional to the stimulus intensity.

• Action Potentials: Triggered at the spike threshold (typically around $-40\,mV$ or $-50\,mV$ relative to a resting potential of $-60\,mV$ to $-80\,mV$). These are binary, non-graded signals used for long-distance conduction.

Synaptic Plasticity

Synaptic plasticity is the durable, activity-dependent modification of synaptic strength.

Types of Plasticity

• Short-term Modulation: Lasts minutes and is reversible.

• Long-term Plasticity: Lasts for hours or days and is stable.

Hebb's Principle

Often summarized as "Neurons that fire together wire together." This is governed by Spike-Timing Dependent Plasticity (STDP):

• Synaptic Strengthening: Occurs when the presynaptic neuron fires before the postsynaptic neuron (\Delta t > 0).

• Synaptic Weakening: Occurs when the presynaptic neuron fires after the postsynaptic neuron (\Delta t < 0).

Molecular Mechanism: The NMDA Receptor

The NMDA receptor acts as a "coincidence detector." To open, it requires:

1. The presence of the neurotransmitter glutamate.

2. Depolarization of the postsynaptic cell (to remove the Mg block).

Process of Potentiation:

1. Activation of NMDA receptors leads to $Ca^{2+}$ influx.

2. Activation of second messengers (e.g., CaMKII, PKC).

3. Insertion of additional AMPA receptors from recycling endosomes into the postsynaptic membrane.

4. This result increases the EPSP (Excitatory Postsynaptic Potential) amplitude (sometimes reaching over $200\%$ of control levels).

Structural Plasticity

Learning and practice (e.g., playing an instrument) lead to physical changes in the brain, such as the growth and reshaping of dendritic spines.

Clinical Relevance of Plasticity

• Adaptive Plasticity: Learning, memory, and recovery from injury.

• Maladaptive Plasticity: Chronic pain, addiction, and PTSD.

General Organization of the Nervous System

Central Nervous System (CNS)

Includes the Brain (Cerebral hemispheres, diencephalon, cerebellum, brainstem) and Spinal Cord. It is the site of analysis and integration of sensory and motor information.

Peripheral Nervous System (PNS)

Consists of cranial and spinal nerves, sensory ganglia, and receptors. It is divided into:

• Somatic Motor System: Controls skeletal (striated) muscles.

• Visceral Motor System (Autonomic): Controls smooth muscles, cardiac muscles, and glands via Sympathetic, Parasympathetic, and Enteric divisions.

Brain Hierarchical Organization

1. Forebrain: Includes the Cerebrum (7), Basal ganglia, and Diencephalon (6).

2. Midbrain: (5).

3. Hindbrain: Includes the Cerebellum (4), Pons (3), and Medulla oblongata (2).

4. Spinal Cord: (1).

Spinal Cord Anatomy

• Segments: Cervical (head, neck, arms), Thoracic (upper trunk), Lumbar (lower torso and legs), and Sacral.

• Enlargements: Cervical and Lumbar enlargements accommodate the high densities of neurons for limbs.

• Axis: Features a rostrocaudal axis. The rostral spinal cord has a higher proportion of white matter (axons), while the caudal spinal cord has a higher proportion of gray matter.

• Internal Structure:

  • Dorsal Horn: Laminae I-VI (sensory input).

  • Ventral Horn: Laminae VII-IX (motor output).

  • Dorsal Root Ganglion: Contains cell bodies of sensory neurons.

Neuronal Microenvironment

The brain is metabolically fragile because it has a high rate of energy consumption (for ion gradient maintenance), low glycogen stores, and suffers rapid damage when ATP is depleted.

The Blood-Brain Barrier (BBB)

Blood is unsuitable for neurons because its pH, ion levels ($K^+$), amino acids, hormones, and cytokines vary. The BBB protects the brain using:

• Tight Junctions: Between endothelial cells of capillaries.

• Astrocytic Endfeet: Surround the capillaries.

• Pericytes: Provide structural and regulatory support.

Transport across BBB:

• $O_2$, $CO_2$, and lipophilic molecules cross via simple diffusion.

• Hydrophilic nutrients (glucose, amino acids) require carrier-mediated transporters.

Circumventricular Organs (CVOs): Areas where the BBB is thin or absent to allow the brain to monitor blood chemistry. These include:

• Subfornical organ (SFO)

• Organum vasculosum of the lamina terminalis (OVLT)

• Posterior pituitary

• Pineal gland

• Median eminence

• Area postrema

• Subcommissural organ

Cerebrospinal Fluid (CSF)

CSF serves three primary functions:

1. Buoyant Support: The density of CSF ($1.007\,g/mL$) is close to the density of the brain ($1.040\,g/mL$), allowing the brain to float and reducing its effective weight.

2. Protection: Acts as a shock absorber.

3. Chemical Homeostasis: Regulates the environment for neurons.

Production and Flow:

• Produced by the Choroid Plexus at a rate of approximately $500\,mL/day$.

• Turnover is approximately $3$ times per day.

• Volume distribution: $30\,mL$ in ventricles and $120\,mL$ in the subarachnoid space.

• Flow: Exits through the foramina of Magendie and Luschka into the subarachnoid space; drained into venous blood via Arachnoid Granulations/Villi.

• Current steady state: Volume remains constant when absorption equals formation.

• Absorption threshold: Absorption begins when CSF pressure exceeds venous sinus pressure (approx $70-100\,mm\,H_2O$).

Choroid Plexus Ion Fluxes:

• Involves transepithelial movement of $Na^+$, $Cl^-$, $HCO_3^-$, and $H_2O$ from the extracellular space across the choroidal epithelium (with apical microvilli and cilia) into the CSF.

• Uses $Na^+/K^+$ ATPase and various cotransporters (e.g., $Na^+/K^+/2Cl^-$) to drive fluid secretion.