Nervous System PDF

Nervous system About this Chapter Organization of the nervous system Electrical signals in neurons Cell-to-cell communication in the nervous system  The Nervous System (NS)  Functions  Sensory function : gathering information  Integrative function...

Nervous system About this Chapter Organization of the nervous system Electrical signals in neurons Cell-to-cell communication in the nervous system  The Nervous System (NS)  Functions  Sensory function : gathering information  Integrative function : processes & interprets sensory input, and decides if action is needed  Motor function : response to integrated stimuli  effectors  The NS is classified by structure & function Structural Classification Functional Classification The integration of all three major functions General Overview The Nervous System  Nervous Tissue: The Neurons Functional cells of the NS  Specialized to transmit stimuli  Consists of:  cell body: nucleus & cell organelles  cytoplasmic extensions from the cell body form  Dendrites  Axons The Nervous System Cells of the Nervous System The general neuron & it’s function The Nervous System Cells of the Nervous System Neurons – Functional Classification 1. Afferent – Conduct APs to the CNS  The Nervous System Cells of the Nervous System Neurons – Functional Classification 2. Interneurons – Conduct APs within the CNS The Nervous System Cells of the Nervous System Neurons – Functional Classification 3. Efferent – Conduct APs to the PNS 1- Overview of Nervous System Organization A. Central Nervous System (CNS) - brain and spinal cord B. Peripheral Nervous System (PNS) – spinal/cranial nerves 1.Sensory (Afferent) Division - TO the CNS a.somatic afferents - from skin, muscle, joints b.visceral afferents - from membranes & organs 2. Motor (Efferent) Division - FROM the CNS a.Somatic Nervous System (Voluntary) - to skeletal muscles b.Autonomic Nervous System (Involuntary) - to organs & glands – i. Sympathetic Division – ii. Parasympathetic Division The Nervous System Cells of the Nervous System Cells are grouped into two functional categories – Neurons Do all of the major functions on their own, are 1. Afferent 2. Interneurons 3. Efferent – Neuroglia Play a supporting role to the neurons Divided into CNS and PNS Neuroglia – CNS – PNS » Astrocytes » Neurolemmocytes » Oligodendrocytes (Schwann cells) » Microglia » Ependymal cells » Satellite cells 2- The Structure of a Neuron (Nerve Cell) Neuron - special cells of nervous system that carry messages in the form of electrical Impulses Supporting Cells of Neurons 1.Support Cells of the CNS (Glial Cells) d. oligodendrocytes - form “myelin sheaths” around axons of CNS; increase speed of impulses  2- The Structure of a Neuron (Nerve Cell), cont 2. Support Cells of the PNS a. Schwann cells form "myelin sheaths" around axons; also assist in regeneration of axon  Special Characteristics of Neurons 1- amitotic - "not mitotic"; they cannot reproduce or regenerate after certain point in life 2- longevity - neurons can survive entire lifetime 3- high metabolic rate - require OXYGEN and GLUCOSE at all times  Neuron Cell Body (soma; perikaryon) 1. major part from which the processes (axons and dendrites) project; 5-140 micron diameter 2. single large spherical nucleus with nucleolus 3. Nissl Bodies - Rough Endoplasmic Reticulum (rER); make proteins and plasma membrane Typical Neuron Processes (Dendrites & Axon), cont c. axolemma - plasma membrane of neuron d. axon hillock - the cone-shaped region of attachment of the axon to the cell body; site where action potential is triggered  Myelin sheath wrap of Scwhann cells (PNS) and oligodendricytes (CNS) around the axon a. increases speed of action potential signal [myelinated (150 m/s); unmyelinated (1 m/s)] b. nodes of Ranvier - gaps between myelin cells at regular intervals on axon Electrical Signals in Neurons  Neurons are electrically excitable due to the voltage difference across their membrane. Electrical Signals in Neurons  Neurons communicate with two types of electric signals:  graded potentials that are used for short- distance communication only (i.e. local membrane changes).  action potentials that can travel over both short and long distances within the body.  (Nerve action potential is called nerve impulse)  As you touch the pen, a graded potential develops in the sensory receptors in the skin of the finger.  The graded potential trigger an action potential which travel to the CNS. Electrical Signals in Neurons  The production of graded potentials and action potentials depends on:  The resting membrane potential.  (an electrical voltage difference across the plasma membrane)  The presence of certain ion channels. Types of Ion Channels  Leakage (nongated) channels  These channels are randomly alternate between open and closed positions (always open).  Nerve cells have more K+ than Na+ leakage channels  Membrane permeability to K+ is higher which explains the resting membrane potential of -70mV in nerve tissue.  Gated channels open and close in response to a stimulus  results in neuron excitability  Gated Ion Channels 1. Voltage-gated channels respond to a direct change in the membrane potential. They participate in the generation and conduction of action potentials. 2. Ligand (chemical)-gated channels respond to a specific chemical stimulus. Chemical ligands include neurotransmitters, hormones and ions. Ligands may act directly (e.g. acetylcholine) or indirectly (e.g. hormones) 3. Mechanically gated ion channels respond to mechanical vibration (sound), pressure or stretching Terminology Associated with Changes in Membrane Potential Polarized: +ve outside and –ve inside at rest Depolarization: tracing moves upwards from rest (becomes more +ve, e.g. Na+ enters cell). Repolarization: tracing moves back to rest (returns to rest, K+ exits cell). Hyperpolarization: tracing moves downwards from rest (becomes more -ve, e.g. K+ exits cell). Graded Potentials  Action Potential Action potential (AP) is a sequence of electrochemical changes that increase membrane potential from resting value of about -70mV to a peak of about +30mV (depolarization), and then return it back to -70mV again (repolarization).  Action Potential Chemical or mechanical stimulus caused a graded potential to reach at least (-55mV or threshold) If graded potential reaches threshold AP occurs (All or none principle). Voltage-gated Na+ channels open & Na+ rushes into cell (Depolarization). only a total of 20,000 Na+ actually enter the cell, but they change the membrane potential considerably(up to +30mV). Positive feedback process. Voltage-gated K+ channels open but slowly & K+ rushes outside cell (Repolarization) The Action Potential: Summarized Potentials in Electrical Signaling The Process Action Potential Formation Membrane is at rest -70mV ECF Chemically gated Na+ channel ICF Potentials in Electrical Signaling Action Potentials – The process – Excitatory stimulus (mechanical, electrical, chemical) applied & activates corresponding Na+ gated channel ECF Chemically gated Na+ channel ICF Potentials in Electrical Signaling Action Potentials – The process – Na+ enters in causing slight depolarization Possibly to threshold ECF Chemically gated Na+ channel ICF Potentials in Electrical Signaling Action Potentials – The process – The Rising phase – If threshold is reached All of the voltage gated Na+ channels will open, increasing membrane permeability some 6000 fold! Causing further depolarization of the membrane to +30 mV ECF V-gated Na+ Channels V-gated Na+ Channels Chemically gated V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Na+ channel ICF Potentials in Electrical Signaling Action Potentials – The process – The falling phase next, slow voltage gated K+ channels open K+ flows down its concentration gradient… Membrane potential falls ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Slow V-gated K+ Slow V-gated K+ Channels Channels Channels Channels ICF Potentials in Electrical Signaling Action Potentials – The process – In the meantime… – The voltage gated Na+ channels have closed (both gates) – Membrane potential continues to fall as K+ continues its outward flow ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Slow V-gated K+ Slow V-gated K+ Channels Channels Channels Channels ICF Potentials in Electrical Signaling Action Potentials – The process – Next the slow voltage gated K+ channels start to close – There is additional K+ that diffuses through during the closing, causing membrane potential to hyperpolarize slightly ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Slow V-gated K+ Slow V-gated K+ Channels Channels Channels Channels ICF  Potentials in Electrical Signaling Action Potentials – The process – The Na+/K+ ATPase restores the resting membrane potential ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Channels Channels ICF  Potentials in Electrical Signaling Action Potentials – The process – The Na+/K+ ATPase restores the resting membrane potential ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Channels Channels ICF ATP  Potentials in Electrical Signaling Action Potentials – The process – The Na+/K+ ATPase restores the resting membrane potential ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Channels Channels ICF ATP ADP  Potentials in Electrical Signaling Action Potentials – The process – The Na+/K+ ATPase restores the resting membrane potential ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Channels Channels ICF  Potentials in Electrical Signaling Action Potentials – The process – The Na+/K+ ATPase restores the resting membrane potential ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Channels Channels ICF  Potentials in Electrical Signaling Action Potentials – The process – The Na+/K+ ATPase restores the resting membrane potential ECF V-gated Na+ Channels V-gated Na+ Channels V-gated Na+ Channels Slow V-gated K+ Slow V-gated K+ Channels Channels ICF  Why does the AP only travel in ONE direction (towards the synapse)? Because the voltage gated Na+ and K+ channels undergo a refractory period  Refractory Period of Action Potential Period of time during which neuron can not generate another action potential. Absolute refractory period even very strong stimulus will not begin another AP inactivated Na+ channels must return to the resting state before they can be reopened Relative refractory period a suprathreshold stimulus will be able to start an AP K+ channels are still open, but Na+ inactivation channels have return to resting state. Propagation of Action Potential  Signal Transmission at Synapses Electrical Chemical Chemical Synapses Chemical Synapses - When an action potential depolarizes the plasma membrane of the synaptic terminal it, - Opens voltage gated Ca channels triggering influx of Ca, - High Ca causes synaptic vesicles to fuse with presynaptic membrane, - Vesicles releases neurotransmitter into synaptic cleft, - Neurotransmitter-receptor binding, - Neurotransmitter is released. Structure of neurotransmitter receptors 1- Ionotropic receptor  Ionotropic receptor Ionotropic receptors form an ion channel pore. When an ionotropic receptor is activated, it opens a channel that allows ions such as Na+, K+, or Cl- to flow  Ionotropic receptor Ionotropic receptors are transmembrane molecules that can “open” or “close” a channel that would allow smaller particles to travel in and out of the cell. As the name implies, IONotropic receptors allow different kinds of ions to travel in and out of the cell. Ionotropic receptors are not opened (or closed) all the time. They are generally closed until another small molecule (called a ligand — In our case, a neurotransmitter) binds to the receptor.  Ionotropic receptors As soon as the ligand binds to the receptor, the receptor changes conformation (the protein that makes up the channel changes shape), and as they do so they create a small opening that is big enough for ions to travel through. Therefore, ionotropic receptors are “ligand-gated transmembrane ion channels”. 2- Metabotropic receptor  Metabotropic receptors through signal transduction mechanisms, often G proteins when a metabotropic receptor is activated, a series of intracellular events are triggered that can also result in ion channels opening but must involve a range of second messenger chemicals.  Metabotropic receptors Metabotropic receptors do not have a “channel” that opens or closes. Instead, they are linked to another small chemical called a “G-protein.” As soon as a ligand binds the metabotropic receptor, the receptor “activates” the G-Protein (it basically changes the G-Protein). Once activated, the G-protein itself goes on and activates another molecule. This new molecule is called a “secondary messenger.” (A secondary messenger is a chemical whose function is to go and activate other particles). Differences in Function Between Ionotropic and Metabotropic Receptors - Ionotropic receptors act very quickly. As soon as a ligand - binds to them, they change shape and allow ions to flow in. But the ligand doesn’t stay in place very long, and the channel closes back very quickly. - Metabotropic receptors, on the other hand, take a little longer - “to do anything” depending on the number of steps (secondary messengers), required to produce a response. - once activated, the secondary messengers can travel throughout the cell and result in a much wider range of responses.  Minimum To Remember - Ionotropic and metabotropic receptors are both ligand gated transmembrane proteins. - Ionotropic receptors change shape when they are bound by a ligand. This change in shape creates a channel that allows ions to flow through. - Metabotropic receptors do not have channels. - Metabotropic receptors activate a G-protein that in turn acivates a secondary messenger, that in turn will activate something else.  Excitatory & Inhibitory Potentials The effect of a neurotransmitter can be either excitatory or inhibitory EPSP it results from the opening of ligand-gated Na+ channels the postsynaptic cell is more likely to reach threshold to give AP IPSP it results from the opening of ligand-gated Cl- or K+ channels it causes the postsynaptic cell to become more negative or hyperpolarized  Removal of Neurotransmitter Diffusion move down concentration gradient Enzymatic degradation acetylcholinesterase Uptake by neurons or glia cells neurotransmitter transporter Summation Spatial Summation Summation of effects of neurotransmitters released from several presynaptic end bulbs onto one neuron Temporal Summation Summation of effect of neurotransmitters released from 2 or more firings of the same end bulb in rapid succession onto a second neuron  Neurotransmitters Small-Molecule Neurotransmitters Acetylcholine (ACh) released by many PNS neurons & some CNS excitatory on NMJ but inhibitory at others inactivated by acetylcholinesterase Amino Acids Glutamate is excitatory neurons in the brain inactivated by reuptake. GABA is inhibitory neurotransmitter for 1/3 of all brain synapses  Small-Molecule Neurotransmitters Biogenic Amines modified amino acids (decarboxylation) catecholamine norepinephrine epinephrine dopamine serotonin  Small-Molecule Neurotransmitters ATP and other purines (ADP, AMP & adenosine) excitatory in both CNS & PNS released with other neurotransmitters (ACh & NE) Gases (nitric oxide or NO) formed from amino acid arginine by NO synthase  Neuropeptides 3-40 amino acids linked by peptide bonds Substance P -- enhances our perception of pain Pain relief enkephalins -- pain-relieving effect by blocking the release of substance P