Organization of the Nervous System. Physiology of neurons and glial cells.

Dr. Ana-Maria Zagrean MD, PhD Lecturer, Physiology & Neuroscience Div.

Nervous system physiology

Organization of the Nervous system. Physiology of neurons and glial cells. Excitability and ionic transport Synaptic transmission in the nervous system. Neurotransmitters. Physiology of the neuro-muscular system Sensation and sensory processing: Physiology of sight. Physiology of hearing. Sensation and sensory processing: Chemical senses: olfaction and taste. Somatic sensory system: Touch & proprioception. Pain.

Recommended bibliography: Guyton & Hall Textbook of Medical Physiology Boron & Boulpaep Medical Physiology Dale Purves Neuroscience, 5th Edition
www.fiziologie.ro azagrean@gmail.com

The Nervous System

Components: brain, spinal cord, nerves, sensory receptors Responsible for sensory perceptions, mental activities, stimulating muscle movements, secretions of many glands Subdivisions Central nervous system (CNS) Peripheral nervous system (PNS) includes Autonomic and Enteric nervous systems

Nervous System Subdivisions

! All elements of the nervous system work closely together in a way that has no clear boundaries.

Nervous System Organization

Organization of the Nervous System: CNS, PNS & ANS

Central nervous system (CNS):

- brain (including cranial nerve II and retina) and spinal cord;

- covered by the meninges (pia mater, arachnoid, and dura mater); - special features: oligodendrocytes provide myelin; axons cannot regenerate

Peripheral nervous system (PNS):

- parts of the nervous system that lie outside the dura mater; - consists of peripheral ganglia (including cell bodies); sensory receptors; afferent & efferent peripheral portions of spinal nerves, cranial nerves (except CN II) and all peripheral portions of ANS. - special features: Schwann cells provide myelin; axons can regenerate

Autonomic nervous system (ANS):

- anatomically includes parts of CNS & PNS; - regulates & controls visceral functions through reflex arcs (visceral afferent/ sensory neurons, control centers in the CNS that receive input, and visceral motor output). - special feature: functionally distinct system

Nervous System: structure

1) CENTRAL NERVOUS SYSTEM (CNS): brain spinal cord 2) PERIPHERAL NERVOUS SYSTEM (PNS): cranial nerves spinal nerves 2 types of nervous tissue cells: neurons: sensory, motor, interneurones/association neurons non-neuronal/neuroglial cells: astrocytes, microglia, oligodendocytes / Schwann cells, ependymal cells

Spinal cord

Genetics and the Brain

Genomics has brought insight into how nuclear DNA provides instructions for the assembly and operation of the brain Human genome: about 20,000 genes (coding & regulatory DNA) 14,000 genes expressed in the developing/mature brain about 8,000 genes are expressed in all cells and tissues a great deal of brain specific genetic information resides in the regulatory DNA sequences that control timing, quantity, variability, and cellular specificity of gene expression individual genes vary in the level of expression in specific brain regions and cells (i.e. the amount of mRNA expressed) foundation of the diversity & complexity of brain functions ! Gene mutations & brain pathology (Huntington D, Alzheimer D, Parkinson D)
Dale Purves, Neuroscience, 5th Ed.

Genetics and the Brain

Genetics & Genomics understand physiopathology develop new therapies But relationship between genotype and phenotype is not just the result of following genetic instructions, and genetic information alone cannot explain how the brain operates in normal individuals, or how disease processes disrupt normal brain functions. the need to understand the cell biology, anatomy and physiology of the nervous system constituent cells and the circuits they form.

Dale Purves, Neuroscience, 5th Ed.

Cells of the Nervous System:

Cellular diversity of the brain

Human brain is estimated to contain 100 billion neurons and several times as many supporting cells glial cells. The nervous system has a greater range of distinct cell types whether categorized by morphology, molecular identity, or physiological activity - than any other organ system

Cells of the nervous tissue

Nerve cells: neurons and neuroglial cells. ~1011 neurons in the human brain and 10 x more neuroglia Neurons have special shapes, physiological properties, and connections
(~1000 synapses/each neuron & other connecting mechanisms !)

information transmission throughout the nervous system unique patterns of connectivity & regional specialization tremendous complexity of NS

Neuroglial cells variable structures that are suited for their diverse functions provide a physiological environment for neurons can function as signaling cells !

12

Typical neuron has 4 regions: cell body, dendrites, axon, presynaptic terminals each region is specialized for its particular function information flows in a single direction

Neuron Cell Body Location Most are found in the central nervous system Gray matter cell bodies and unmylenated fibers Nuclei clusters of cell bodies within the white matter of the central nervous system Ganglia collections of cell bodies outside the central nervous system

The structure of a typical neuron

(1) cell body/ soma /perikaryon (nucleus, ER, Golgi complex, mitochondria) (2) dendrites of various complexity: tapered, limited length, contain membrane rec. for neurotransmitters; dendritic spines
The dendrites & cell body are the main areas for receiving information through the membrane receptors that bind and respond to the neurotransmitters released by neighboring cells.

(3) the axon: - a cone-shaped axon hillock, an initial segment/ the spike initiation zone (unmyelinated region where AP initiates) - axon can extend for more than a meter, +/- myelin (electrical insulation, fast impulse spread), high density of Na+ channels - contain axoplasm, microtubules and microfilaments that confer structural stability and axonal transport (4) the presynaptic terminals: rapid conversion of the neuron's electrical signal into a chemical / another signal in the postsynaptic membrane.

Neuronal compartmentalization
Neurons, as polarized cells, have distinct membrane protein at each of the distinct domains of the plasma membrane. Smooth and rough ER & Golgi system (are absent in the axon). Protein synthesis (mainly in the cell body, less in dendrites). Role of mitochondria. Anterograde and retrograde axoplasmic transport of molecules in vesicles along microtubules is mediated by MAPs (microtubule-associated proteins): kinesin for anterograde transport (always move
toward the plus end of microtubules, away from the cell body) and dynein for retrograde transport (provides a mechanism for target-derived growth factors, as NGF, to reach the nucleus of a neuron where it can influence survival !).
Quantum content

Features of Axoplasmic Transport Transport Type Speed (mm/day) Mechanism Saltatory movement along microtubules by the motor molecule kinesin (ATP dependent)

Material Transported Mitochondria Vesicles containing peptide and other neurotransmitters, some degradative enzymes

Fast ~ 400 anterograde

Fast retrograde

~200-300 Saltatory movement Degraded vesicular along microtubules membrane by the motor Absorbed exogenous molecule dynein (ATP material (toxins, viruses, dependent) growth factors) Not clear; possibly by Cytoskeletal elements molecular motors (e.g., neurofilament and microtubule subunits) Soluble proteins of intermediary metabolism Actin

Slow ~0.2-8 anterograde

"signaling endosome"

Axoplasmic Transport

Classification of neurons based on their structure (Borone)

Various forms of neurons. A. Pyramidal cell from the cerebral cortex. B. Cerebellar Purkinje cell. C. Sympathetic postganglionic neuron. D. Spinal cord motor neuron. E. Dorsal root ganglion cell. a - axon

Neuroglial cells of the central nervous system. A. Fibrous astrocyte (glial foot processes in association with a capillary). B. Protoplasmic astrocyte. C. Oligodendrocyte (each process is responsible for the production of one or more myelin sheath internodes around central axons. D. Microglial cell. E. Ependymal cells.

Classification of Neurons

Classification of Neurons based on their function

Sensory (afferent) neurons Carry impulses from the sensory receptors -Cutaneous sense organs -Proprioceptors detect stretch or tension Motor (efferent) neurons -Carry impulses from the central nervous system Interneurons (association neurons) -Found in neural pathways only in the central nervous system -Connect sensory and motor neurons

Classification of neurons based on their function

Types of neurons: Sensory or afferent Interneurons Motor or efferent

Sensory/afferent nerves: messages from periphery to CNS Motor/efferent nerves: messages from CNS to peripheral tissues.

Neuron Classification

Classification of neurons based on the type of information transmitted

Direction of information flow: Afferent (sensory): neurons that transmit information into the CNS from sensory cells or sensory receptors outside the nervous system (dorsal root ganglion cell and neurons in the sensory nucleus of the fifth cranial nerve). Interneurons: relay or association neurons Efferent (motor): neurons that transmit information out of the CNS to muscles or secretory cells (spinal motor neurons and motor neurons in the autonomic nervous system). Anatomical distribution of the information flow: Visceral: neurons that transmit information to or from internal organs or regions that arise embryologically from the branchial arch (e.g., chemoreceptors of the carotid body). Somatic: neurons that transmit information to or from all nonvisceral parts of the body, including skin and muscle. Embryological origin of the structure being innervated: Special: neurons that transmit information to or from a "special" subset of visceral or somatic structures - special visceral neurons: information travels to or from structures derived from the branchial arch region of the embryo (e.g., pharyngeal muscles) - special somatic neurons, which handle only sensory information: the neurons arise from the organs of special sense (e.g. retina, taste receptors, cochlea).

Characteristics of Neurons
1) excitable

- respond to stimuli - produce & conduct electrical impulses - release chemical regulators
2) amitotic- cannot divide by mitosis ! 3) long-lived 4) high metabolic rate

Non-neuronal Cells

neuroglia support & protect & nourish & signal smaller & numerous types:
astrocytes microglia Schwann cells * oligodendrocytes * ependymal cells

Non-neuronal cells: Schwann cells and oligodendrocytes (PNS) (CNS)

Myelin
-Layers of lipid membrane of oligodendrocytes (CNS) or Schwann cells (PNS) -The signal that causes these glial cells to myelinate the axons is an epidermal GF-like ligand (neuregulin), which derives from the axon and whose potency is dependent of axonal size (usually axons > 1 micrometer in diameter are myelinated ) - voltage-gated Na+ channels are highly concentrated in the nodes of Ranvier, and in low density beneath the sheath of myelin AP jump from one Ranvier to the next one saltatory conduction increased conduction velocity: 3-120 m/sec in myelinated axons comparing to 0.5-2 m/sec in unmyelinated axons

Myelin, Oligodendrocyts and network of intercellular channels between astrocytes (A) and oligodendrocytes (O)

Orthmann-Murphy, J. L. et al. J. Neurosci. 2007;27:13949-13957

Neuro-vascular unit

Neuron astroglia connections