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Neuroscience Lecture: Cellular Components, Neural Circuits, and Organization

Genetics and Genomics in the Nervous System

  • The nervous system (NS) is the product of gene expression.
  • Color legend (from the transcript visuals): blue = nervous system selective expression; purple = genes expressed in all tissues; peach = genes expressed in other tissues.
  • Current estimates:
    • 20{,}000 genes in the genome.
    • 14{,}000 genes expressed in the NS (≈ 70\%).
  • Gene categories:
    • Coding genes
    • Non-coding genes: often involved in controlling levels and timing of expression
    • Introns
    • 5′ and 3′ regions (promoters, enhancers, and regulatory elements)
  • Regulation of gene expression is differential throughout the NS, leading to spatial and temporal variation in transcript and protein levels.
  • Concept of gene expression across NS: individual genes can show region-specific expression patterns (illustrated by dots at different locations with varying color intensities). Expression levels can be represented as Gene → mRNA → Protein relationships.
  • Implications for neural development and function: spatially and temporally regulated expression underlies cellular diversity and circuit formation.
  • Example of consequence of NS gene mutations: mutations in NS-expressed genes can lead to malformations and/or functional deficits in neural cells.
    • ASPM (Abnormal Spindle-like Microcephaly-associated) mutation affects mitotic spindle-associated protein and is linked to microcephaly (reduced brain size).
  • Broader relevance: genetic and genomic regulation informs understanding of neurodevelopmental disorders and potential therapeutic targets.

Cellular Components of the Nervous System

  • Major cell types:
    • Neurons: diverse morphologies, shown via Golgi staining (silver stain labeling entire cell body) used by Camillo Golgi and Santiago Ramón y Cajal; Golgi staining contributed foundational work to modern neuroscience.
    • Glial cells: astrocytes, oligodendrocytes, microglia, glial stem cells, oligodendrocyte precursors, ependymal cells, satellite cells.
  • Golgi stain and historical context:
    • Developed by Golgi (1843–1926) and popularized by Cajal (1852–1934), who is often called the Father of Modern Neuroscience.

Neurons: Morphology and Basic Features

  • Major structural components:
    • Soma (cell body): contains nucleus, Golgi apparatus, ribosomes, mitochondria.
    • Dendrites: receive inputs; can be highly branched.
    • Axon: conducts action potentials; initial segment near the soma; axon hillock; myelination; synaptic endings (boutons).
  • Axon structures:
    • Axon hillock and initial segment: site of action potential initiation.
    • Myelination: increases conduction velocity along the axon; produced by oligodendrocytes in CNS and Schwann cells in PNS.
    • Synaptic endings (boutons): presynaptic and postsynaptic terminals; historically linked to the Reticular Theory (note: modern view emphasizes synaptic specialization).
    • Node of Ranvier and internodes: gaps in myelin that facilitate saltatory conduction.
  • Dendrite and soma diagrams: various neuron morphologies demonstrated (e.g., unipolar, pseudounipolar, bipolar, multipolar).
  • Unipolar and pseudounipolar neurons: peripheral axon projects to skin/muscle with a central axon projecting into the CNS; typical of certain sensory pathways.
  • Bipolar neurons: two processes (one dendrite, one axon).
  • Multipolar neurons: many dendrites and a single axon; most CNS neurons are multipolar.

Neuron Structural Diversity

  • Dendrites and soma organization:
    • Basal dendrites (from the base of the soma) and apical dendrites (extending from the top).
  • Multipolar neuron types: numerous variations in dendritic trees and axon projections, enabling a broad range of processing capabilities.

Functional Regions of Neurons

  • Four functional regions producing distinct signals:
    • Input region
    • Integrative region
    • Conductive region
    • Output region
  • Model motifs:
    • Sensory neuron (input from receptors)
    • Motor neuron (output to muscles)
    • Local interneuron (local circuit processing)
    • Projection interneuron (connects distant regions; often excitatory via projection neurons or inhibitory via interneurons)
    • Neuroendocrine cell (neurosecretory functions)
  • Examples of circuit organization include relationships to capillaries and local networks.

Glial Cells of the Nervous System

  • Major glial cell types and roles:
    • Astrocyte (A): star-shaped cell; maintains microenvironment; contributes to the blood-brain barrier; participates in construction of new synapses; subset maintains stem cell properties in adults.
    • Oligodendrocyte (Oligo): myelinates axons in the CNS; speeds electrical conduction; contrasted with Schwann cells in the PNS which myelinate peripheral nerves.
    • Microglial cell: innate immune cells of the CNS; sentinels; macrophage-like; secrete cytokines to communicate with immune and other cells; precursors can arise from other microglia or migrate from damaged vasculature.
    • Glial stem cell: subset of astrocytes; located in subventricular zone near blood vessels and ventricles; capable of self-renewal and giving rise to multiple cell types in a tissue.
    • Ependymal cells: line the ventricles and choroid plexus; produce and move cerebrospinal fluid (CSF); help move CSF and monitor its composition and pressure; specialized ependymal cells contribute to CSF production.
    • Oligodendrocyte precursor: not a stem cell in the strict sense; precursor to oligodendrocytes and some astrocytes.
    • Satellite cells: peripheral nervous system support cells located in dorsal root ganglia housing somatic sensory neurons; provide metabolic support and protection.
  • Expression patterns:
    • Different cell-types (astrocytes, oligodendrocytes, microglia) can express distinct gene sets, contributing to their specialized roles in the NS.
  • Summary of glial roles in NS health and function:
    • Structural support, myelination, immune surveillance, CSF dynamics, synapse formation and remodeling, and local homeostasis.

Neural Circuits

  • Neural circuits describe groups of neurons acting together.
  • Classic example: knee-jerk (myotatic) reflex circuit, involving:
    • Afferent (sensory) pathway
    • Efferent (motor) pathway
    • Muscle pairs: extensor and flexor muscles
  • Circuit components:
    • Projection neurons (long-range excitatory or inhibitory connections)
    • Local neurons (short-range interneurons)
    • Interneurons (connective neurons within a local circuit)
  • Functional dynamics: circuits can be simplified into sensory input → processing by interneurons and projection neurons → motor output, with excitatory and inhibitory synapses shaping the response.

Electrophysiology and Neural Signals

  • Action potentials (spikes): the fundamental electrical signals that propagate along neurons.
  • Recording approaches:
    • Extracellular vs intracellular recordings
    • Microelectrode arrays used to measure membrane potentials
  • Basic recording scenario (illustrative):
    • Stimulus invokes membrane potential changes (APs) in neurons; membrane potentials are recorded over time (ms scale).
  • Example sequence in a simple circuit:
    • Sensory neuron receives input -> membrane potential changes -> interneuron integrates and modulates -> motor neurons drive effector muscles; excitatory synapses increase activity, inhibitory synapses decrease it.
  • Key concepts:
    • Membrane potential changes reflect synaptic potentials and action potentials.
    • Activation of excitatory synapses leads to depolarization; inhibition leads to hyperpolarization.

Organization of the Nervous System: CNS vs PNS

  • Central Nervous System (CNS):
    • Brain
    • Spinal cord
    • Functions: integration of motor and sensory information
  • Peripheral Nervous System (PNS):
    • Sensory components
    • Motor components: somatic motor nerves and visceral motor system (autonomic nerves)
  • Diagrammatic relationships: CNS and PNS connect to create integrated responses.

Peripheral Nervous System Details

  • Somatic division: senses (skin, muscle, joints) and motor control of skeletal muscles; dorsal root ganglia (DRG) house somatic sensory neurons.
  • Autonomic nervous system (ANS): motor control of viscera, smooth muscle, and glands; two antagonistic divisions:
    • Sympathetic division: stimulation (fight-or-flight responses)
    • Parasympathetic division: relaxation and restoration (rest-and-digest)

Neural Pathways and Pathway Organization

  • DRG and spinal cord organization: white matter and gray matter distributions; genetic engineering can illuminate neural pathways.

Functional Analysis: Receptive Fields

  • Receptive field: the area in which stimuli influence the firing of a neuron.
  • Center-surround organization: excitation in center, inhibition in surround (and vice versa depending on cell type).
  • Higher-order neurons integrate converging inputs from many peripheral neurons; some are excited, others inhibited by the same stimulus,
    and the combined information is transmitted to higher-order neurons for processing.

Five Principles of Organization in the Nervous System

1) Functional systems involve multiple brain regions that carry out different information-processing tasks.

  • Typical sensory pathway example: sensory neuron → thalamus → primary sensory cortex → secondary sensory cortex → …
  • At each stage, information is processed and transmitted to the next stage.
  • Information is carried by two cell types: projection neurons (convey information; excitatory) and interneurons (local contacts; inhibitory).

2) Identifiable pathways connect components of a functional system.

  • Axons bundled into pathways; pathways tend to be located in roughly the same brain region across individuals.
  • Pathways are identifiable and traceable.

3) Topographic maps are formed.

  • A topographic map is a point-to-point neural representation of a body area.
  • In sensory systems: peripheral receptor positions are preserved from periphery to cortex; also reflects receptor density.
  • In motor systems: neurons regulating specific body parts are clustered together; motor maps are not uniform for all body parts.

4) Functional systems are hierarchically organized.

  • Information processing flows in a rank-ordered sequence through brain regions.
  • At each level, convergence occurs; cells respond to more selective information as you ascend the hierarchy.
  • Visual system example:
    • Thalamus (LGN): neurons respond to spots of light.
    • Visual cortex: single cell integrates inputs from many LGN cells and responds to bars of light with specific orientation.
    • Association cortex: convergence of multiple primary visual inputs; cells respond best to particular orientations moving in a direction.
    • Higher up, cells respond to shapes or objects (e.g., faces).

5) Sensory and motor activities on one side of the body are mediated by the opposite cerebral hemisphere (contralateral control).

  • Bilateral and symmetrical organization with crossovers (decussation) occurring at different anatomical levels.
  • Concept example: contralateral control of movement and sensation is a fundamental organizational principle of many NS pathways.

Homunculus and Topographic Maps

  • Homunculus: a traditional representation of the body as mapped onto the brain.
  • It is a topographic map of somatic senses but not a strict one-to-one representation of every body part.
  • Significance: emphasizes orderly, regionally specific cortical representation and cortical plasticity.

Connections to Broader Neuroscience Themes

  • Linkages to developmental biology: gene expression patterns influence neuronal differentiation and circuit assembly.
  • Clinical relevance: understanding mutations (e.g., ASPM) can inform neurodevelopmental disorder etiology and potential therapies.
  • Ethical and practical considerations: genetic interventions require careful evaluation of risks, benefits, and societal implications.
  • Real-world relevance: foundational principles of organization underlie neuroimaging interpretation, neuroprosthetics design, and neural rehabilitation strategies.

Key Terms to Remember

  • Neuron types: unipolar, pseudounipolar, bipolar, multipolar.
  • Axon regions: axon hillock, initial segment; nodes of Ranvier; internodes; myelination.
  • Dendritic architecture: basal vs apical dendrites; dendritic branching patterns.
  • Glial cell types and roles: astrocyte, oligodendrocyte, microglia, glial stem cell, ependymal cells, satellite cells, oligodendrocyte precursor.
  • Receptive field organization: center-surround; excitation vs inhibition.
  • Five Principles of Organization: hierarchical processing, identifiable pathways, topographic maps, hierarchical organization, contralateral control.

Notable Figures and Historical Context

  • Golgi staining (silver stain) used to visualize entire neuron morphology; foundational for neuron doctrine.
  • Cajal’s work refined our understanding of synaptic connectivity and neural circuits.
  • Conceptual tools like the homunculus and topographic maps originate from systematic mapping of brain-body relationships.

Quick Reference Equations and Numbers

  • Gene counts and NS expression:
    • 20{,}000 total genes; 14{,}000 NS-expressed genes (≈ 70\%).
  • Other numerical references include the existence of multiple cell types with region-specific expression and 5′/3′ regulatory regions, but exact numeric counts beyond those are not provided in the transcript.

Connections to Earlier and Later Content

  • This material connects molecular genetics with cellular anatomy (neurons and glia) and systems neuroscience (neural circuits, CNS vs PNS, and organizational principles).
  • The vocabulary and concepts prepare for more advanced topics such as synaptic physiology, neurodevelopment, and functional imaging analyses.