Nervous System I: Structure and Function

Introduction and General Functions of the Nervous System

The nervous tissue is essential as it satisfies the structural and functional requirements of the organism. The nervous system is organized to detect changes, known as stimuli, in both internal and external environments. Once this information is detected, the system evaluates it and subsequently responds by initiating changes in muscles or glands. There are three general functions that form the basis of its operation:

1. Detección de Cambios (Stimuli): The nervous system utilizes specialized cells, known as sensory neurons (neuronas sensitivas), and sensory receptors to perceive a wide variety of environmental or internal changes. This detection is the initial step in responding to stimuli.
2. Evaluación de Información: Once detected, information is transmitted to the Central Nervous System (SNC), which consists of the brain (encéfalo) and the spinal cord (médula espinal). The SNC serves as the structural and functional center that integrates sensory input components and evaluates them. Complex functions such as thinking and memory are executed by neurons, specifically through interneuron circuits.
3. Respuesta a Estímulos: Following evaluation, the nervous system generates a response by transmitting nerve impulses to effector cells, which are either muscular or glandular. Motor neurons (neuronas motoras) conduct these impulses from the SNC to the effectors. Upon reaching the synapse with an effector cell, a neurotransmitter (chemical messenger) is released to trigger a response, such as muscle contraction or glandular secretion.

Structural and Functional Subdivisions of the Nervous System

Given its complexity, the nervous system is classified in several ways to facilitate understanding. The classic structural classification is based on macroscopic dissections and divides the tissue based on its position in the body: central or peripheral.

Sistema Nervioso Central (SNC): This is the structural and functional hub of the entire system. It includes the brain and spinal cord. Within the SNC, gray matter (sustancia gris) contains dendrites, neuronal cell bodies, unmyelinated axons, and neuroglia. Clusters of neuronal cell bodies in the gray matter of the brain and spinal cord are called nuclei. White matter (sustancia blanca) surrounds the gray matter in the spinal cord and is composed of bundles of myelinated axons organized into tracts or pathways (vías).

Sistema Nervioso Periférico (SNP): This consists of all nervous tissue outside the SNC. Its components include cranial nerves, spinal nerves, ganglia (clusters of neuronal cell bodies outside the brain and spinal cord), plexuses (complex neuronal networks, such as those formed by the ventral rami of spinal nerves), and sensory receptors. For example, dorsal root ganglia contain sensory neuron cell bodies that carry information to the spinal cord. In the SNP, bundles of axons, connective tissue, and blood vessels are called nerves.

Functional classifications focus on the direction of impulses:

• División Aferente (Sensory): Consists of all pathways carrying information toward the SNC. Sensory neurons transmit impulses to the spinal cord or brain; some of this reaches the cerebral cortex for conscious perception (e.g., touch or pain).
• División Eferente (Motor): Comprises all pathways carrying information from the SNC toward effectors (muscles or glands).

Further functional classification is based on the types of effector organs controlled:

• Sistema Nervioso Somático (SNS): Carries motor information to somatic effectors (skeletal muscles). It is involved in voluntary movements like walking or maintaining posture. A single myelinated somatic motor neuron axon extends directly from the SNC to the skeletal muscle fibers it innervates, forming the "final common pathway."
• Sistema Nervioso Autónomo (SNA): Also known as the visceral nervous system, it operates without voluntary control. Its efferent pathways conduct impulses to autonomous effectors: smooth muscle (in internal organs), cardiac muscle, and glands. Most autonomous motor pathways involve two neurons in series: a preganglionic neuron (cell body in the SNC) and a postganglionic neuron (cell body in a ganglion outside the SNC). It is subdivided into sympathetic and parasympathetic divisions.

The Enteric Nervous System (SNE)

Often called the "digestive brain," the SNE is an extensive neuronal network distributed from the esophagus to the anus. It contains approximately $100 \times 10^6$ neurons, a number comparable to the spinal cord. It can function independently of the SNC. The SNE is organized into two primary plexuses:

• Plexo Mientérico (Auerbach): Located between the longitudinal and circular smooth muscle layers, it regulates the frequency and force of muscular contractions (motility).
• Plexo Submucoso (Meissner): Located within the submucosa, it innervates secretory cells of the epithelial mucosa to control secretions.

Nervous Tissue: Neurons and Neuroglia

Neurons (Structure): Neurons are the fundamental functional units and are electrically excitable cells. They generate and conduct nerve impulses (action potentials).

• Cell Body (Soma/Pericarion): The central part containing the nucleus and organelles. Notable are Nissl bodies (cuerpos de Nissl), which are condensations of rough endoplasmic reticulum (RER) used for protein synthesis for growth and repair.
• Dendrites: Short, highly branched extensions that serve as the main receiving structure. They receive stimuli that activate ion channels, generating graded potentials.
• Axon: A single, thin, cylindrical structure that propagates impulses away from the cell body. It joins the soma at the axon hillock (cono axónico). The "trigger zone" (zona gatillo) is typically at the junction of the axon hillock and the initial segment where impulses originate. Axons may be covered by a myelin sheath (vaina de mielina). Ends branch into telodendrons (axones terminales) which finish in synaptic end bulbs (bulbos sinápticos terminales) or varicosities containing synaptic vesicles with neurotransmitters.
• Cytoskeleton: Contains neurofibrils consisting of intermediate filaments for support.

Types of Neurons:

• Multipolar: Several dendrites and one axon; most common in brain/spinal cord and all motor neurons.
• Bipolar: One main dendrite and one axon; found in the retina, inner ear, and olfactory pathway.
• Unipolar (Pseudounipolar): A single process that divides into a central and a peripheral branch; these are always sensory neurons.
• Functional Classification: Sensory (afferent), Motor (efferent), and Interneurons (association neurons located within the SNC to process sensory info).

Neuroglia: These support cells are $5$ to $25$ times more numerous than neurons and can divide mitotically.

• SNC Neuroglia:     - Astrocytes: Provide structural support, form the Blood-Brain Barrier (BHE), regulate extracellular $K^+$ levels, capture excess neurotransmitters, and form scar tissue after injury.     - Oligodendrocytes: Form myelin sheaths around multiple axons in the SNC.     - Microglia: Small phagocytic cells that remove debris and microbes.     - Ependymal cells: Line liquid-filled cavities (ventricles); produce and circulate cerebrospinal fluid (LCR).
• SNP Neuroglia:     - Schwann cells: Form the myelin sheath and the neurolemma around peripheral axons; facilitate slow regeneration.     - Satellite cells: Surround and support neuronal cell bodies in SNP ganglia.

Synapses and Electrical Communication

A synapse is the region where signals pass from a presynaptic neuron to a postsynaptic cell (neuron or effector).

• Chemical Synapse: Presynaptic and postsynaptic cells are separated by a synaptic cleft (hendidura sináptica) filled with interstitial fluid.     - Mechanism: Impulse arrives -> $Ca^{2+}$ enters through voltage-gated channels -> exocytosis of synaptic vesicles -> neurotransmitter binds to ligand-gated receptors -> graded potential (post-synaptic potential) generated.
• Electrical Synapse: Cells are directly joined by gap junctions (uniones comunicantes) containing tubule-like connexons. This allows ions to flow directly between cells.     - Advantages: Faster communication (no neurotransmitter delay) and synchronization (useful for the heart and visceral smooth muscle).

Membrane Potentials and the Action Potential

Cells depend on electrical excitability. This requires a Resting Membrane Potential (PMR) and specific ion channels.

• Ion Channels:     - Passive: Open/close randomly.     - Ligand-gated: Open in response to chemical stimuli (neurotransmitters).     - Mechanically-gated: Open in response to physical stimuli (touch/pressure).     - Voltage-gated: Open in response to potential changes; crucial for action potentials.
• Resting Membrane Potential (PMR): Usually $-70\,mV$ (negative inside). Maintained by unequal ion distribution, impermeable anions, and $Na^+/K^+$ ATPase pumps.
• Action Potential (PA): An "all-or-none" rapid fluctuation. To start, a stimulus must depolarize the membrane to a threshold (umbral) of approximately $-59\,mV$.     - Phases:         - Depolarization: Voltage-gated $Na^+$ channels open; $Na^+$ influx makes inside positive.         - Repolarization: $Na^+$ channels inactivate; voltage-gated $K^+$ channels open; $K^+$ efflux restores negativity.         - Hyperpolarization: Excessive $K^+$ efflux briefly makes the potential more negative than RMP.
• Conduction: Continuous (in unmyelinated axons) vs. Saltatory (in myelinated axons, jumping between Nodes of Ranvier). Speed increases with myelin, larger axon diameter, and warmer temperatures.

Neurotransmitters and Clinical Significance

There are over $50$ known neurotransmitters. They can be excitatory (generate PPSE - Potencial Postsináptico Excitatorio) or inhibitory (generate PPSI - Potencial Postsináptico Inhibitorio). Removal occurs through reuptake, enzymatic degradation, or diffusion.

Small Molecule Transmitters:

• Acetilcolina (ACh): Excitatory at neuromuscular junctions; inhibitory at the heart (decreases rate). Inactivated by acetylcholinesterase (AChE).
• Amines: Derived from amino acids (Tyrosine, Tryptophan, Histidine). Includes Serotonin (memory/mood), Dopamine (motor control/mood; deficiency causes Parkinsonism), and Catecholamines (Adrenaline/Noradrenaline).
• Amino Acids: Glutamate (main excitatory transmitter, accounts for $75\%$ of excitatory synapsis in the brain), GABA, and Glycine (inhibitory).
• Nitric Oxide (NO): A gas produced on demand from arginine. Lasts less than $10\,\text{seconds}$. Involved in memory/learning.

Neuropeptides (Large Molecules): Chains of $2-40$ amino acids. Examples: Substance P (pain), Enkephalins/Endorphins (natural analgesics/pain suppression during labor), Cholecystokinin (CCK - appetite suppression). They often act as neuromodulators.

Clinical Relevance: Most diseases are chemical disorders involving neurotransmitters. Parkinson’s disease results from dopamine deficiency. Epilepsy involves abnormal electrical discharges. Understanding synapses is vital for drug development, as pharmacological agents often modify the synthesis, release, or receptor binding of neurotransmitters.