The Human Nervous System

• The human nervous system comprises a complex network of neurons assisted by glial cells
• Each neuron has hundreds of interconnections for information processing and response generation
• Nerve tissue is distributed throughout the body as an integrated communications network
• The nervous system has two major divisions: the central nervous system (CNS) and the peripheral nervous system (PNS)
• Central nervous system (CNS) consists of the brain and the spinal cord
• Peripheral nervous system (PNS) consists of cranial, spinal, and peripheral nerves and ganglia
• Nerves conduct impulses to and from the CNS
• Ganglia refers to small aggregates of nerve cells outside the CNS
• Two kinds of cells comprise central and peripheral nerve tissue: neurons and glial cells
• Neurons have long processes
• Glial cells have short processes, support and protect neurons, and participate in neural activities, neural nutrition, and defense of cells in the CNS
• Neurons respond to stimuli by altering the ionic gradient across their plasma membranes
• Cells that can rapidly change potential in response to stimuli, like neurons and muscle cells, are excitable or irritable
• Neurons reverse the ionic gradient promptly in response to stimuli with membrane depolarization, which spreads across the neuron's plasma membrane
• The propagation, called the action potential, the depolarization wave, or the nerve impulse, travels long distances along neuronal processes
• The nerve impulse is transmitted to other neurons, muscles, and glands
• By collecting, analyzing, and integrating information in signals, stabilizes the intrinsic conditions of the body within normal ranges and maintains behavioral patterns
• The Intrinsic conditions of the body is blood pressure, O2 and CO2 content, pH, blood glucose levels, and hormone levels
• Behavioral patterns include feeding, reproduction, defense, and interaction with other living creatures

Development of Nerve Tissue

• The nervous system develops from the ectoderm, the outermost of the three early embryonic layers
• Development begins in the third week
• Signals from the notochord causes the ectoderm to thicken and form the epithelial neural plate
• The sides of the neural plate fold upwards and fuse to form the neural tube, the precursor to the CNS

General Organization of the Nervous System

• Functionally, the nervous system consists of the sensory division (afferent division) and motor division (efferent division)
• The sensory division can also be divided into somatic or visceral actions
• Somatic is sensory input perceived consciously
• Visceral is sensory input not perceived consciously
• The motor division can also be divided into somatic or autonomic sections
• Somatic actions involve motor output controlled consciously or voluntarily
• Autonomic actions involve motor output not controlled consciously
• The autonomic nervous system (ANS) is comprised of autonomic motor nerves which all utilize pathways involving two neurons
• The two neurons involved are a preganglionic neuron (cell body in the CNS) and a postganglionic neuron (cell body in a ganglion)
• The ANS has two divisions: parasympathetic and sympathetic
• Parasympathetic division maintains normal body homeostasis and has ganglia within or near the effector organs
• Sympathetic division controls the body's responses during emergencies and excitement and has ganglia close to the CNS
• ANS components located in the wall of the digestive tract are sometimes referred to as the enteric nervous system

Neurons

• Neurons are the functional units in the CNS and PNS
• Neurolemma is a special name for the cell membrane of neurons
• Neurons have three main parts: the cell body, the dendrites, and the axon
• Cell body is also called the perikaryon or soma
• Nucleus and most of the cell's organelles are located in the cell body
• Serves as the synthetic/trophic center for the entire neuron
• Dendrites are the elongated processes extending from the perikaryon and specialized to receive stimuli
• Stimuli are received from other neurons at unique sites called synapses
• The axon is a single long process ending at synapses
• Specialized to generate and conduct nerve impulses to other cells such as nerve, muscles, or gland cells
• Axons may also receive information from other neurons, mainly modifying the transmission of action potentials
• Neurons and nerve fibers vary in size and shape
• Cell bodies can be very large, measuring up to 150 μm in diameter
• Neurons can be classified according to the number of processes extending from the cell body: multipolar, bipolar, unipolar/pseudounipolar, and anaxonic

Types of Neurons

• Multipolar neurons each have one axon and two or more dendrites
• They are the most common type
• Bipolar neurons have one dendrite and one axon
• They comprise the sensory neurons of the retina, the olfactory epithelium, and the inner ear
• Unipolar/pseudounipolar neurons includes all other sensory neurons
• These have a single process that bifurcates close to the perikaryon
• The longer branch extends to a peripheral ending and the other towards the CNS
• Anaxonic neurons have many dendrites and no true axon
• They do not produce action potentials
• They regulate electrical changes of adjacent CNS neurons
• Because it is difficult to classify neurons structures by microscopic inspection because the fine processes emerging from cell bodies are seldom visible

Nervous Components

• Nervous components are subdivided functionally into sensory neurons (afferent), and motor neurons (efferent)
• Sensory neurons receive stimuli from receptors throughout the body
• Motor neurons send impulses to effector organs such as muscle fibers and glands
• Somatic motor nerves are under voluntary control and typically innervate skeletal muscle
• Autonomic motor nerves control the involuntary or unconscious activities of glands, cardiac muscle, and most smooth muscle
• Interneurons establish relationships among other neurons, forming complex functional networks/circuits in the CNS
• Interneurons comprise 99% of all neurons in adults and are either multipolar or anaxonic
• Most neuronal perikarya occur in the gray matter in the CNS while their axons are concentrated in the white matter
• Terms refer to the general appearance of unstained CNS tissue
• In the PNS, cell bodies are found in ganglia and in some sensory regions(olfactory mucosa)
• Axons are bundled in nerves

Parkinson's Disease

• Parkinson disease is a slowly progressing disorder that affects muscular activity with symptoms that include tremors, reduced facial muscle activity, and loss of balance
• It is caused by gradual loss by apoptosis of dopamine-producing neurons whose cell bodies lie within the nuclei of the CNS substantia nigra
• It is treated with L-dopa (L-3,4-dihydroxyphenylalanine) a precursor of dopamine that augments the declining production of neurotransmitters

Cell Body (Perikaryon or Soma)

• Neuronal cell body contains the nucleus and cytoplasm
• It acts as the trophic center, producing most cytoplasm for the processes
• Most cell bodies are in contact with a great number of nerve endings conveying excitatory or inhibitory stimuli
• Neurons have a large, euchromatic nucleus with a prominent nucleolus
• The cytoplasm of perikarya often contains free polyribosomes and highly developed RER, indicating active production of both cytoskeletal and secretory proteins
• Histologically, these regions with concentrated RER and other polysomes are basophilic, and are distinguished as chromatophilic/Nissl substance/Nissl bodies
• Vary in amount with type/functional state of neuron
• Golgi apparatus is located in the cell body, but mitochondria are found throughout the cell
• Microtubules, actin filaments, and intermediate filaments are abundant
• Neurofilaments are intermediate filaments formed by unique protein subunits
• Impregnated with silver stains, neurofilaments are referred to as neurofibrils
• Some nerve cell bodies also contain inclusions of pigmented material, such as lipofuscin

Dendrites

• Dendrites are short, small processes emerging and branching off the soma
• Usually covered with synapses, dendrites are the principal signal reception and processing sites on neurons
• Dendrites allow a single neuron to receive and integrate signals from nerve cells
• Unlike axons, dendrites become much thinner as they branch, with cytoskeletal elements predominating in these distal regions
• Synapses on dendrites in the CNS occur on dendritic spines membrane protrusions
• Serve as the initial processing sites for synaptic signals
• Depend on actin filaments, and change continuously as synaptic connections on neurons are modified
• Dendritic spines are important in the constant changes of neural plasticity that occurs during embryonic brain development and underlies adaptation, learning, and memory

Axons

• Neurons have only one axon, typically longer than its dendrites
• Axonal processes vary in length and diameter depending on neuron type.
• The plasma membrane of the axon is often called the axolemma and its contents are known as axoplasm
• Axons originate from a pyramid-shaped region of the perikaryon(axon hillock)
• The axolemma has concentrated ion channels
• The action potential is generated in this segment
• Excitatory and inhibitory stimuli algebraical sums
• Axons branch less profusely than dendrites
• They do undergo terminal arborization
• Interneurons and some motor neurons have major branches called collaterals that end at smaller branches with synapses
• Each axonal branch ends with a terminal bouton at a synapse
• Axoplasm contains mitochondria, microtubules, neurofilaments, and transport vesicles

Transport

• Lively bidirectional transport of molecules occurs within axons
• Organelles and macromolecules synthesized in the cell body move by anterograde transport along axonal microtubules via kinesin from the perikaryon to the synaptic terminals
• Retrograde transport in the opposite direction along microtubules via dynein carries certain other macromolecules, such as material taken up by endocytosis, from the periphery to the cell body
• Anterograde/retrograde transports occur rapidly, ~50-400 mm/d
• There is a slower anterograde stream where the movement of the exoskeleton takes roughly to the rate of axon growth, moving only a few millimeters per day

Nerve Impulses

• Nerve impulse/action potential, travels along an axon
• Electrochemical process initiated at the axon hillock when impulses received at the cell body/dendrites meet a threshold
• It is propagated along the axon as a wave of membrane depolarization produced by voltage-gated Na+/K+ channels in the axolemma to allow diffusion into/out of the axoplasm
• Extracellular: Thin zone immediately outside, formed by enclosing glial cells to regulate ionic contents
• Unstimulated neurons
• ATP-dependent Na-K pumps & other membrane proteins maintain an axoplasmic Na+ concentration to 1/10 of outside the cell and a K+ level many times greater than the extracellular
• This produces a ~-65 mV potential electrical difference across the axolemma, with the inside negative to the outside
• Difference is the axon’s resting potential
• irl Local anesthetics interfere with sodium ion influx by binding to he voltage-gated sodium channels of the axolemma

Nerve Impulses Continued

• Once the threshold is met, channels at the axon’s initial segment open and allow a very rapid influx of extracellular Na+ that makes the axoplasm positive in relation to the extracellular environment and shifts resting potential from negative to positive
• After the membrane depolarizes, voltage-gated Na+ channels close and open those for K+ then returns the membrane to its resting potential within milliseconds
• Depolarization stimulates adjacent portions of the axolemma to depolarize/return immediately to the resting potential which causes a nerve impulse or depolarization, to move rapidly along the axon
• After a refraction period, the neuron is ready to repeat and generate an action potential
• Impulses arriving at synaptic nerve endings promote neurotransmitter discharge
• Discharge stimulates/inhibits action potentials in a neuron/non-neural cell

Synaptic Communication

• Synapses are sites of nerve impulse transmission from one neuron to another, or from neurons and other effector cells with unidirectional transmission(electrical to chemical signal)
• Most act by releasing neurotransmitters(small molecules bind receptor proteins then initiates a second-messenger cascade or open/close ion channels)
• Has three components:
• Presynaptic axon terminal (terminal bouton) contains mitochondria/synaptic vesicles
• Synaptic vesicles from neurotransmitter released by exocytosis
• Presynaptic axon terminal contains receptors for the neurotransmitter, and ion channels or other mechanisms to initiate a new impulse
• 20- to 30-nm-wide intercellular space called the synaptic cleft separates membranes
• Impulse opensbriefly calcium channels at presynaptic region then promoting Ca2+ influx that triggers neurotransmitter release by exocytosis immediately
• Released neurotransmitter molecules diffuse across synaptic cleft and binds receptors at the postsynaptic region producing either an excitatory/inhibitory effect

Excitatory/Inhibitory Effects

• Excitatory has neurotransmitters from excitatory synapses open postsynaptic Na+ channels
• Na+ influx initiates a depolarization wave
• Inhibitory has neurotransmitters open Cl- or another channels
• Anion influx/hyperpolarization of cell's the membrane is more negative
• Interplay between excitatory/inhibitory effects on postsynaptic allows synapses to process/fine-tune effector reaction
• Synapses modify impulses passing from presynaptic neurons to postsynaptic cells by similar connections with others
• Response in postsynaptic neurons by summation of activity at hundreds of synapses
• Figure 9-6b has synapse morphological types from CNS

Neurotransmitters

• The chemical transmitter used between neuromuscular junctions and in synapses is acetylcholine, although within CNS other transmitters are included.
• Important actions of common neurotransmitters are summarized in Table 9-1.
• Same transmitter can have different receptors/systems
• After transmitters are released, they are removed quickly by enzyme breakdown, glial activity, or by recycling

Medical Application - Neurotransmitters

• Normally, levels that are available in the cleft for the binding of postsynaptic receptors are regulated by local mechanisms
• For example, SSRIs have been designed to help the reuptake that has been specifically inhibited at the serotonin membrane (that way, neurotransmitters can be augmented at the membrane of serotonergic(CNS) synapses)(widely used to treat disorders of anxiety and depression disorders)

Glial Cells

• These cell supports neural survival and activities
• In mammalian brain, it is x10 more abundant than neurons
• Most cells develop from neural in the embryonic plate
• IN CNS, they surround large neuronal bodies that often surround the renal bodies and processes the processes the axons and dendrites between neurons
• Very Small collagen is within the CNS tissue and these cells subs in to some respects connect the tissue where it creates micro environments to the neural cells
• Fibrous inter cell networks of CNS resembles that of collagen but is actually the fine cellular processes emerging from neuronal and dial
• These processes are collectively called the neuropil (Figure 9-8)
• These glia cells have 6 forms , four in the CNS and two in the PNS: and there main functions + orgins that are summarized in Table 9-2:
• The CNS : 1- Oligodendrocytes 2- astrocytes 3- epididymal cells 4. Microglia -PNS: 1-schwarn cells 2-sateliete cells

Glia Cell: Oligodendrocytes

• Processes extend while others that become sheetlike wrap around a nearby axon (CNS process-Figure 9 – 9a)
• Cytoplasm moves (growing Extension (Figure 9 – 9a)
• Most cytoplasm move (growing Extension
• Cell membranes compacted- myelinated
• Axo fully covered-the myelin sheath is electrical insulated an helps the CNS nerve impluses more rapid Oligodendrocytes are in white matter-high lipids
• These sheaths and processes are not visible to routine microscope light, which is why they might appear as un sustained cytoplasm

Glia CEills: Astrocytes

• For CNS, the processes has a number of star-astyr processes( figure 9-9a and and the astrocytic procceses that are thened by filaments-GFAP protein which creates a unique cell
• Processes occupied a large dynamic Volume- millions
• These mediate many functions

Functions of the CNS regions:

– Extend that cover synapses affect formations function/ plasiticity – Regulae extracellula rionic concentrations – Guide and support different CNS locations – Fibers process from capillaires as move between capillaries-Figure 9– 9a – Forem a barrier protoplasmic layer which likes meninges external surface – Proliferation to form astrocytic scars Finally communicat to anther cellular networks

Medical Application:

• Most brain tumours arrises the fibrous sites
• These have been paths diagnised by expressing GFAp

Glia: Epididymal cells

• Columnar cubic in forms-that lining CNS spinal cord for fluids
• Some CNS-apical cilia movement+ microvilli absorption-Figure 9–9a

Glia Microglia

• Body is Small, less is more numerious, though still more are neurons (9. -12)
• Throughout region these processes interact which synapse (10 fold of cellbody to synaptic probe)
• They also the mechanisms of immune defense
• Unlike other Cells, these do not originate from progenitor cells the circulating macrophages.

Astroglial

Types of Synapses

• Axosomatic Synapse: Branched Axon to neurons cell or Somas, transmit a nerve impulse.
• Transmit
• Axodendritic synapse.: Axon Terminal, and Transmit a nerve impulse, another
• Axoaxonic: Less Frequent. Axons form the synapse, modualtes

The Layers of the Spinla Chord

A. Outer Molecular: Neurl pil, scattered B. Middle has cells of Parkins, and dendrites (and fibers) C aTHICK ANDINNER GRANULAR HAS LITTLE NERUL

SpincalChord

• Has Two Projection( Posterior and Anterior) Gray Comissure around Small Canel

SpinalChord A, P

• A(astrocytes), aBUNDANT CELL BODIES, especially of motor Neurons
• P Contains Oligdendrocytes and tracts (axon)

CNS(The Layers+ Brain)

• Completely covered in tissue , the meningitis, contains a high collage
• Has organized areas -w matter/g matter
• White: myelinated+ axons and oligodendricytes present( but neurons are very little)
• Gray: Has neurons and their and synapses where and it contains abundant (but neutrons are very little)