Fundamentals of the nervous system

The Nervous system is the master controlling and communicating system of body • Cells communicate via electrical and chemical signals • Rapid and specific • Usually cause almost immediate responses

Three overlapping functions 1. Sensory input - information from sensory receptors about internal and external changes 2. Integration - processing and interpretation of sensory input 3. Motor output - activation of effector organs (muscles and glands) to produce a response

Divided into two principal parts: • Central nervous system (CNS) • Brain and spinal cord of dorsal body cavity • Integration and control center • Interprets sensory input and dictates motor output • Peripheral nervous system (PNS) • The portion of nervous system outside CNS • Consists mainly of nerves that extend from brain and spinal cord • Spinal nerves to and from spinal cord • Cranial nerves to and from brain

Peripheral nervous system (PNS) has two functional divisions • Sensory (afferent) division • Somatic sensory fibers: convey impulses from skin, skeletal muscles, and joints to CNS • Visceral sensory fibers: convey impulses from visceral organs to CNS

Peripheral nervous system (PNS) has two functional divisions • Motor (efferent) division • Transmits impulses from CNS to effector organs - muscles and glands • Somatic nervous system • Autonomic nervous system

Neurons are the “Hallmark Cells” of Nervous Tissue (along with Glia cells) • They receive, process, transmit, and exchange information • Electrically excitable and communication within the cell is achieved by electrical signals (graded potentials and action potentials

Connected with each other to form neuronal networks • Neurons connect via synapses, which are points of cell-cell communication with chemical signals (neurotransmitters)

Neurons are metabolically and structurally supported by Glia cells

Glia cells fill the space in the central nervous system (CNS) that is not occupied by neurons • They are essential for the function of neurons and the nervous system • Control and regulate extracellular environment (homeostasis) • Limit diffusion of release neurotransmitters to synaptic target regions • Act as mechanical scafoolding to “guide” developing neurons to their targets • Electrical insulation of neurons for better signal conduction

Astrocytes: • Fill space between neurons • Influence neurite formation during development and growth • Neurotransmitter receptors (respond to neuronal activity) • Interface neurons with blood capillaries • Control chemical content of extracellular space surrounding neurons • buffer neurotransmitters • regulate ion concentrations • release growth factors

Schwann Cells and Oligodendrocytes • Form electrical insulation around neurons by wrapping membrane layers around neurites • Myelin Sheath critical for efficient electrical signal transmission in most neurons Oligodendrocytes - Found in CNS - One glia cell interacts with multiple neurons Schwann Cells - Found in PNS - One glia cell targets one neuron

Oligodendrocytes - Branched cells, whose processes wrap CNS fibers, forming insulating myelin sheaths in thicker nerve fibers

Microglial cells - Function as phagocytes and clean up debris in the nervous system Non-neuronal cells in nervous tissue - Blood Vessels - Connective Tissue - Ependymal Cells, lining of brain ventricles and spinal canal

The nervous system is made up of discrete cells called neurons (nerve cells) • Nerve fibers are the cellular processes of neurons • Axons • Dendrites • Connections between neurons are made by contact to other neurons or cells • Synapses • Preferred direction of signal transmission from cell to cell • From axon of presynaptic cell to dendrite of postsynaptic cell • Neuron can receive both excitatory and inhibitory input • Each type will come from a different presynaptic cell connection

Neurons are specialized cells and contain typical organelles like all other cell types • Phospho-lipid bilayer membrane (plasmalemma) • Nucleus • Mitochondria (oxidative catabolism) • Ribosomes (protein synthesis) • Smooth and rough endoplasmic reticulum (protein synthesis, storage, and transport) • Golgi apparatus (vesicle packaging) • Microtubules (cytoskeleton, transport pathways) • Myosin (transport pathways) • Actin (cytoskeleton, transport pathways)

Unique to Neurons is their strong anatomical and functional polarization by neurites

Dendrite (postsynaptic “Input” side of a neuron) • Several dendrites can originate from soma with extensive branching • Postsynaptic membrane is specialized to receive presynaptic chemical signals (neurotransmitters) • Conveys incoming messages toward cell body as graded potentials (short distance signals) • In many brain areas, finer dendrites are highly specialized to collect information and contain dendritic spines

Axon (the presynaptic “Output” side of the neuron) • Transports electrical signals to postsynaptic target cells • Axon can be a few μm to over one meter • Axon Hillock is where the axon originates from the cell body • Axon can branch into Axon Collaterals • Terminates in presynaptic Bouton • forms synapse with postsynaptic dendritic spine of another neuron • contain synaptic membrane vesicles filled with neurotransmitters

Neurons come in a wide variety of anatomical shapes Number of neurites • Unipolar, Bipolar, Multipolar Kind of Connections Made • Motor Neurons • Sensory Neurons • Interneurons

Contact point between the presynaptic cell and postsynaptic cell • Axon bouton and dendritic spine - Synaptic transmission is the information transfer between the two cells - Occurs across the synaptic cleft (~20 nm) - Neurotransmitters are released from presynaptic neuron and travel across the synaptic cleft to the postsynaptic cell by diffusion - Postsynaptic membrane has receptors that bind to neurotransmitters and generate an electrical signal response

Neurotransmitters are the messenger molecules released by exocytosis from presynaptic neurons • Diffusion across the synaptic cleft is relatively slow -passive transport-, but it is over a relatively short distance Different chemical classes of neurotransmitters: Amino Acids, Amines, peptides

Synaptic transmission requires a pool of synaptic vesicles that are loaded with neurotrasmitters and ready for release in the axon terminal • Neurotransmitters are released by EXOCYTOSIS, i.e. fusion of vesicle with presynaptic membrane! (Active Transport)

What Triggers NT Release from Presynaptic Neuron?

Presynaptic neurons generate action potentials that travel down the axon and arrives at axon terminal (①). • Action potential depolarization OPENS Voltage-gated Ca2+ channels • Ca2+ enters the presynaptic neuron (②) • Ca2+ causes neurotransmitter vesicles to DOCK (③) and FUSE (④) with axon membrane • Exocytosis of neurotransmitter • Neurotransmitter released in synaptic cleft and diffuses to postsynaptic cell

Ionotropic Receptors are Ligand-Gated Ion Channels • Binding of neurotransmitters (Ligand) OPENS ion channels - Generates an excitatory response – depolarization of postsynaptic membrane - Generates an inhibitory response - hyperpolarization of postsynaptic membrane Result: GRADED Postsynaptic Potential - EPSP = Excitatory Postsynaptic Potential - IPSP = Inhibitory Postsynaptic Potential

Amplitude of EPSP/IPSP reflects presynaptic excitation / release of neurotransmitters • Combined input from many synapses, made with the same or different presynaptic cells ONLY Graded potentials allow information summation and processing of synaptic events by - Spatial Summation - Temporal Summation - Any Combination of Both Integration can happen at a single synapse, synapses within same dendritic segment, at dendritic branching, and in the soma