Chapter 6: Neuronal Signaling and the Structure of the Nervous System Flashcards
6.1 Structure and Maintenance of Neurons
BACKGROUND
NERVOUS SYSTEM:
- made up of the CENTRAL NERVOUS SYSTEM (CNS; the brain and the spinal cord) and the PERIPHERAL NERVOUS SYSTEM (PNS; neurons outside the central nervous system, nerves that connect the brain and spinal cord with the body’s muscles. glands, sense organs, and other tissues)
NEURON:
- the basic cellular unit of the nervous system (the functional unit)
a. function by generating electrical signals that move from one part of the cell to another part of the cell itself or other cells; the electrical signal causes the release of neurotransmitters to communicate with other cells
b. CELL BODY (AKA SOMA) and DENDRITES (including DENDRITIC SPINES): regions that receive information from other neurons; CELL BODY includes the nucleus and ribosomes, so has genetic information and machinery for protein synthesis; DENDRITES are branched outgrowths that receive incoming information from other neurons; DENDRITIC SPINES are protrusions from DENDRITES that increase the surface area of DENDRITES and help them send messages
c. AXON: begins at the AXON HILLOCK (initial segment) and ends at AXON TERMINAL; AXON carries outgoing signals; transmits information to the other neurons or effector cells; AXON TERMINAL releases neurotransmitters across extracellular gap to other cells
GLIA CELLS:
- non-neuronal cells that do not directly participate in signaling but play supporting roles for neurons
- surround the axon and dendrites of neurons, provide nourishment, sever as “nerve glue”
MYELIN SHEATH:
- insulating sheath formed over certain neurons in the CNS and PNS that speeds transmission of signals; made of membranes of SCHWANN CELLS (PNS) or OLIGODENDROCYTES (CNS) that are interrupted periodically at NODES OF RANVIER; MYELIN speeds up conduction and conserves energy
a. MYELIN is made up of 20-200 layers of plasma membrane
b. SCHWANN CELLS makes individual myelin sheaths in the PNS; are a type of glial cell
c. OLIGODENDROCYTES are a type of glial cell that works in the CNS to to branch and form myelin around up to 40 axons
d. NODES OF RANVIER are spaces between adjacent sections of myelin where the axon’s plasma membrane is exposed to extracellular fluid
e. AXONAL TRANSPORT is when various organelles/materials/nutrients are moved along length of axon by specific motor proteins
NEUROTRANSMITTERS:
- chemical mediators released by neurons that act as signals between neurons or between neurons and other cells (e.g. muscle cells
ALONG THE AXON THERE IS:
dendrites- branches off of cell body, receives information
cell body- receives information, genetic info. and machinery
axon hillock- connects cell body to axon; initiates signals
axon- sends signals –> axon collateral- side branches that send signals to others
axon terminal- end of axon, end of outward signal
6.2 Functional Classes of Neurons
BACKGROUND
AFFERENT NEURONS:
- transmit information into the CNS from receptors at their peripheral endings
- at their peripheral ends (farthest from the CNS) afferent neurons have SENSORY RECEPTORS that respond to physical or chemical changes in their environment by generating electrical signals in the neuron
a. note- receptor can have two definitions: 1 specialized portion of the plasma membrane or separate cell closely associated with neuron ending; 2 specific proteins a chemical messenger combines with to exert its effects on a target cell
- afferent neurons have a distinct shape from what is normally expected of axons; the axon divides after leaving the cell body- one branch (peripheral process) begins where the afferent terminal branches converge from the receptor endings, the other branch (central process)enters the CNS to form junctions with other neurons; BOTH THE CELL BODY AND THE LONG AXON (peripheral part) ARE OUTSIDE THE CNS AND ONLY A PORTION ENTERS THE CENTRAL PROCESSES OF THE BRAIN OR SPINAL CORD
EFFERENT NEURONS:
- transmit information out of the CNS to effector cells
- have the usual shape
- (some exceptions) CELL BODIES AND DENDRITES ARE IN THE CNS AND THE AXONS EXTEND OUT TO THE PERIPHERY
EFFERENT AND AFFERENT NEURONS
- GROUPS OF EFFERENT AND AFFERENT NEURON AXONS, TOGETHER WITH MYELIN, CONNECTIVE TISSUE, AND BLOOD VESSELS FORM THE NERVES OF THE PNS
INTERNEURONS:
- LIE ENTIRELY WITHIN CNS; form circuits with other interneurons or connect afferent and efferent neurons
- account for 99% of all neurons
- connect neurons within the CNS
SYNAPSE:
- specialized junction between a neuron and a target cell across which signals are sent by neurotransmitters
- one neuron alters the electrical and chemical activity of another
- most occur between axon terminal of one neuron and dendrite or cell body of another
- neuron can be presynaptic to one cell and postsynaptic to another
a. PRESYNAPTIC NEURON: a neuron that conducts a signal toward a synapse
b. POSTSYNAPTIC NEURON: a neuron that conducts a signal away from a synapse
6.3 Glial Cells
BACKGROUND
GLIAL CELLS:
- nonneuronal cells of the CNS and PNS, including astrocytes, oligodendrocytes, microglia, and ependymal cells
- neurons account of less than half of cells in the human CNS
- surround the axon and the dendrites of neurons and provide physical and metabolic support, and act as “nerve glue”
- pathophysiology- most neurons can’t divide, but glial cells can, so CNS tumors originate from glial cells vs. neurons
- different types of glial cells and different functions
1. oligodendrocytes- CNS glial cell, forms myelin sheath for CNS neurons
2. schwann cells- PNS glial cells, have properties of CNS glia, produce myelin sheaths of peripheral neurons’ axons
3. astrocytes- CNS glial cell, regulate composition of extracellular fluid of CNS, removes K+ ions and neurotransmitters around synapses, stimulate formation of tight junctions; these tight junctions form the BLOOD-BRAIN BARRIER which acts as selective filter for substances exchanged between blood and other tissues; astrocytes also sustain CNS neurons metabolically by providing glucose/removing waste; in embryos, astrocytes help secrete growth factors and get cells to final destinations; they also capacities to generate weak electrical responses to take part signaling to the brain
3. microglia- CNS glial cell, specialized macrophage-like cell that performs immune functions and aids with neuroplasticity
4. ependymal cells- line fluid cavities of the brain and spinal cord to regulate production and flow of cerebrospinal fluid
a. help regulate the extracellular fluid composition b. sustain the neurons metabolically c. form MYELIN d. form that BLOOD-BRAIN BARRIER (selective filter for materials entering the CNS) e. serves as guides for developing neurons f. provide immune functions g. regulate the production of CEREBROSPINAL FLUID
6.4 Neural Growth and Regeneration
BACKGROUND
GROWTH AND DEVELOPMENT OF NEURONS
- Neurons develop from stem cells, migrate to their final locations, and send out processes to their target cells
a. In the embryo, undifferentiated stem cells develop into neurons or glia. once cell division is over, the neuronal daughter cells differentiate, go to their final locations, and begin developing their axons and dendrites. GROWTH CONES make tips for developing axons and help the axons find their correct route/target. as the axon develops, it is guided along cell surfaces and molecular influences move the axon to the right target; SYNAPSES FOR WHEN THE TARGET OF THE ADVANCING GROWTH CONE IS REACHED
b. GROWTH CONE: specialized enlargement that forms the tip of an extending axon and that functions to direct a growing axon to find its final destination
- MICROCEPHALY: occurs when fetuses have severely underdeveloped brains (as in the case with ZIKA VIRUS) because of damage to fetal developing nervous system by things like viruses, malnutrition, alcohol, etc.
- In development of nervous system, many neurons and synapses degenerate (apoptosis), likely to fine-tune messaging pathways
- Cell division that forms new neurons and the PLASTICITY that enables remodeling of neural tissue after injury markedly decrease between birth and adulthood; brain modifies its structure and function in response to stimulus or injury; can be development of new neurons or synaptic connections; basic CNS structure does not change once formed, but growth and learning in aging is due to this plasticity
- Damaged peripheral neurons may REGROW THE AXON TO THEIR TARGET NEURON, but functional regeneration of severed CNS axons does not usually occur
a. axons can repair themselves and restore functions if damage occurs outside of CNS and does not affect the cell body; part of axon still attached to cell body gets GROWTH CONE and grows out to the effector organ to restore function (only 1mm a day, however)
b. however, if the cell body is affected and the axon is separated from it, the cell body degenerates
interesting stuff: spinal injuries typically crush, rather than cut, tissue; spinal injuries have problem of preventing apoptosis of oligodendrocytes; researchers are trying to find out how to promote regrowth of severed axons, etc.
QUESTIONS: why outside the CNS to regrow?
6.5 Basic Principles of Electricity
- Separated electrical charges that are allowed to come together create an ELECTRICAL POTENTIAL, the potential to do work
a. electrical potential is also called a POTENTIAL DIFFERENCE, because it refers to the difference in the amount of charge between two points
b. the units of electrical potential are volts; potential differences are measured in millivolts
c. the distribution of the charged particles on either side of the plasma membrane causes electrical difference that aids in signal integration and cell-to-cell communication
CURRENT:
- occurs when charge particles flow in a net direction
- it is the movement of electrical charge
- the electrical potential between charges tends to make them flow producing a current
- opposite charges= attract, so current will bring them together; like charges= repel, so current will increase the separation between them
- the MAGNITUDE of a current depends on the potential difference between charges and on the nature of the material or structure that they are moving through
- The lipid bilayer of the plasma membrane creates RESISTANCE to movement of electrical charge (it acts as an insulator that keeps charged ions separated); this also called hindrance to the electrical charger
a. OHM’S LAW relates potential (measured in volts, V) to resistance (R) and current (I) such that I = V/R
b. resistance = high, current = low
c. INSULATORS–> HIGH ELECTRICAL RESISTANCE AND REDUCE CURRENT FLOW; CONDUCTORS –> LOW RESISTANCE AND RAPID CURRENT FLOW - Ionic current flows readily in the aqueous intracellular and extracellular fluids
a. extracellular fluid- solutes are mainly sodium and chloride ions; Na+ & Cl-
b. intracellular fluid- solutes are mainly potassium ions and ionized nonpenetrating molecules like phosphate compounds and proteins with negatively charged side chains ; K+, PO4 3-
C. WATER WITH DISSOLVED IONS IS A RELATIVELY GOOD CONDUCTORS (INTRACELLULAR AND EXTRACELLULAR FLUIDS HAVE MANY IONS AND THEREFORE CAN CARRY CHARGE WELLS; HOWEVER, THE LIPID LAYERS OF THE PLASMA MEMBRANE ARE REGIONS OF HIGH ELECTRICAL RESISTANCE THAT SEPARATE THE INTRACELLULAR AND EXTRACELLULAR FLUID)
KNOW HOW TO USE OHM’S LAW
6.6 The Resting Membrane Potential
RESTING MEMBRANE POTENTIAL:
- at rest, neurons have a potential difference across their plasma membranes, with the inside being negatively charged with respect to the outside of the cell
- electrical potential difference across a plasma membrane of an unstimulated cell
a. generated mainly by ion concentration differences across the membrane and the membrane’s relative permeabilities to those ions
b. abbreviated Vₘ
c. relative to the extracellular fluid or the outside of the cell to determine the excess charge; measures the difference in charge across a membrane
- resting membrane potential of neurons is generally -40 to -90 mV; this number is typically steady unless there are changes in an electrical current that alter the potential, however, this would no longer be resting
- tiny excesses of negative ions within the cell and positive ions outside of it cause the resting membrane potential; the excesses of opposite charges are attracted to each other; surfaces of the cell membrane within and without have positive charges lining outside and negative lining inside to create potential while majority of charges of intracellular and extracellular fluid are actually balanced
ION CONCENTRATION DIFFERENCES:
- the magnitude of resting membrane potential depends mainly on two factors: 1. differences in specific ion concentrations in the intracellular and extracellular fluid; 2. differences in membrane permeabilities to the different ions
- Na+, K+, and Cl- are present in the highest concentrations in regards to flow across membranes; Na+ and Cl- have lower concentrations within the cell but higher without; K+ has a lower concentration without the cell and a higher concentration within
Ion Extracellular Intracellular
Na+ 145 mmol/L 15 mmol/L
Cl- 100 7
K+ 5 150
EQUILIBRIUM POTENTIAL:
- membrane potential at which the concentration and electrical forces on an ion are equal in magnitude and opposite in direction
a. can be calculated for any ion by the NERST EQUATION
- The equilibrium potential for one ion can be different in magnitude and direction from those of other ions depending on the concentration gradients between the intracellular and extracellular compartments for each ion; NERST tells you how much electrical force would balance the tendency of an ion to diffuse down its concentration gradient
steps to understanding equilibrium potential:
0. (setup) there are two compartments separated by a membrane that is permeable to only 1 ion (channel); there is 0.15 M of NaCl one side and KCL on the other side.
1. there is no potential difference across the membrane because the two compartments contain equal numbers of positive and negative ions; though the positive ions are different, the total number of positive ions is the same across the containers. 2. then, a K+ channel is opened (there is no Na+ channel); K+ will diffuse down its concentration gradient from comp. 2 to comp. 1. Na+ ions cannot move across the membrane; K+ ions moving to comp. 1 makes comp. 1 have excess of + charge and comp. 2 have excess of - charge. A POTENTIAL DIFFERENCE IS CREATED ACROSS THE MEMBRANE. as the charges inc. on each side, the potential influences the action of the K+. the K+ is attracted to the - charge on its original side (comp. 2) and the positive charge in comp. 1 tends to repel the K+ ions out of comp. 1
3. there is now an electrochemical gradient. as long as the flux of K+ ions down the gradient is more than the flux due to membrane potential, the net flux of K+ will be from comp. 2 to comp. 1
4. Eventually, however, the membrane potential becomes negative enough to cause a fluz equal but opposite to the flux produced by the concentration gradient; THE MEMBRANE POTENTIAL AT WHICH THESE TWO FLUXES BECOME EQUAL IN MAGNITUDE BUT OPPOSITE IN DIRECTION IS CALLED THE EQUILIBRIUM POTENTIAL; there is no net movement of the ion because the opposing fluxes are equal and the potential will no longer change
THE AMOUNT OF IONS NECESSARY TO ACCOMPLISH THIS IS MINISCULE IN COMPARISON TO THE AMOUNT ACTUALLY WITHIN THE CELL
CONTRIBUTION OF DIFFERENT ION PERMEABILITIES
- when membrane channels for many different ions are open at the same time, permeability and concentration gradients for all the ions must be considered when accounting for the membrane potential
- for a given concentration gradient, the greater the membrane permeability of one type of ion, the greater the contribution that ion will make to the membrane potential
- At rest, LEAK CHANNELS in the plasma membrane are much more available for K+ than Na+, so the membrane potential is close to the K+ equilibrium potential
a. membrane potential can be calculated by the GHK EQUATION as long as the concentrations of all the ions can cross the membrane through channels are known, as well as their relative permeabilities; The GOLDMAN-HODGKIN-KATZ EQUATION is essentially an expanded version of the NERST equation that takes individual ion permeabilities into account
- CONTRIBUTIONS OF NA+, K+, AND CL- TO OVERALL MEMBRANE POTENTIAL ARE A FUNCTION OF THEIR CONCENTRATION GRADIENTS AND RELATIVE PERMEABILITIES
- THE CONCENTRATION GRADIENTS DETERMINE THEIR EQUILIBRIUM POTENTIALS, AND THE RELATIVE PERMEABILITY DETERMINES HOW STRONGLY THE RESTING MEMBRANE POTENTIAL IS INFLUENCED TOWARD THOSE POTENTIALS
***RESTING POTENTIAL IS GENERATED ACROSS THE PLASMA MEMBRANE LARGELY BECAUSE OF THE MOVEMENT OF K+ OUT OF THE CELL DOWN ITS CONCENTRATION GRADIENT THROUGH CONSTITUTIVELY OPEN K+ CHANNELS CALLED LEAK CHANNELS, MAKING THE CELL NEGATIVE WITH RESPECT TO THE OUTSIDE. NA+ ALSO HAS SOME IMPACT, AND DOES PULL SLIGHTLY TOWARD NA+ EQUILIBRIUM. ION CHANNELS ALLOW NET MOVEMENT OF NA+ INTO THE CELL AND K+ OUT OF THE CELL.
- Plasma membrane Na+/K+-ATPase pumps maintain low intracellular Na+ concentration and high intracellular K+ concentration by active transport***
CONTRIBUTION OF ION PUMPS
- The Na+/K+-ATPase pumps directly contribute a small component of the potential because they are ELECTROGENIC
- leak channels contribute the majority to determining resting membrane potential
a. ELECTROGENIC PUMP means that that the pump moves a net charge across the membrane and contributes directly to the membrane potential
- the Na+/K+-ATPase pump pumps 3 Na+ out of the cell for every 2 K+ it pumps in; this is the direct contribution that makes the inside of the cell more negative
SUMMARY:
- in a steady state resting neuron, the flux of ions across the membrane reaches a dynamic balance in which K+ is highly permeable but has a small electrochemical gradient and Na+ has low permeability but a large electrochemical gradient. In this state, the inward and outward currents are equal, so the membrane potential rests at a steady value.
- the negative potential for Cl- is equal to the resting membrane potential
QUESTION: get the resting membrane potential differences explained to me? like huh
- Neurons are excitable- that is, they are capable of being electrically excited and generating action potentials
a. EXCITABILITY: the ability to produce electrical signals that can transmit information between different regions of the membrane; membranes that have this property are called EXCITABLE MEMBRANES; all neurons and muscle cells are excitable membranes
b. DEPOLARIZATION: a change to a less negative potential than the resting level
c. OVERSHOOT: a reversal in the membrane potential polarity such that a neuronal membrane becomes positive inside with respect to the outside of the cell
d. HYPERPOLARIZATION: a change to a more negative potential
e. REPOLARIZATION: a return to the resting potential following a depolarization - changes in membrane permeability to ions causes the changes in membrane potential that the neuron uses as signals
ELECTRICAL SIGNALS
GRADED POTENTIALS:
- local potentials with magnitudes that can vary and that die out within 1 To 2 nm of their site of origin (that is, they are DECREMENTAL)
- changes in membrane potential confined to a relatively small region of the plasma membrane
- the magnitude of the potential can vary
- charge flows between the places of origin of the potential and the adjacent regions of the plasma membrane
- can be either depolarizing or hyperpolarizing
- due to open leak channels, the change in membrane potential decreases as the distance increases from the initial site of the potential change
- though small stimulus will die out over distance, if additional stimulus is added before the potential has completely died away, these can add to the graded potential from the first stimulus
- a potential change of variable amplitude and duration that is conducted decrementally; has no threshold or refractory period
- given names based on the location of the potential or function they perform; three types-
1. receptor- a graded potential produced at the peripheral endings of afferent neurons (or in separate receptor cells) in response to a stimulus
2. synaptic- a graded potential change produced in the postsynaptic neuron in response to the release of a neurotransmitter by a presynaptic terminal; may be depolarizing (an excitatory postsynaptic potential or EPSP) or hyperpolarizing (an inhibitory postsynaptic potential or IPSP)
3. pacemaker- a spontaneously occurring graded potential change that occurs in certain specialized cells
- often mediated by LIGAND-GATED ION CHANNELS (response to binding of signaling molecules) and MECHANICALLY GATED ION CHANNELS (response to physical deformation of plasma membrane)
ACTION POTENTIAL:
- large alternations in the membrane potential; may change as much as 100 mV
- response is often due to VOLTAGE-GATED ION CHANNELS (especially NA+ AND K+)
- rapid, all-or-none (non-graded) change in membrane potential during which the membrane depolarizes and then repolarizes
a. provides long-distance transmission of information through the nervous system
b. occurs in excitable membranes because these membranes contain many VOLTAGE-GATED CHANNELS
c. begins as Na+ channels open, moving the membrane potential toward the Na+ equilibrium potential
d. ends as Na+ channels INACTIVATE and K+ channels open, leading to an AFTERHYPERPOLARIZATION and, as K+ channels close, returns to resting conditions
e. can be triggered by depolarizing graded potentials in sensory neurons, at synapses, or in some cells by pacemaker potentials
- voltage-gated Na+ channels:
1. respond faster to changes in membrane voltage; when area of membrane is depolarized, the Na+ channels open before the K+ channels do and close faster;
2. INACTIVATION GATE; ball and chain limits flux of Na+ by blocking the channels shortly after it opens; allows channel to go back to closed after opening
THRESHOLD POTENTIAL:
- the potential for initiation of the depolarizing phase of an action potential, when voltage-gated Na+ channels open in large numbers
- a membrane potential at which an action potential is initiated
REFRACTORY PERIODS:
- the time during and immediately following an action potential when the membrane is absolutely or relatively refractory to initiation of a new action potential
- ABSOLUTE REFRACTORY PERIOD: during an action potential, no matter how strong a stimulus is, a second action potential will not be generated; either Na+ channels are already open or have proceeded to the inactivated state from the first action potentials; the inactivation gate that has blocked these channels must be removed by repolarizing the membrane and closing the pore before the channels can reopen to a second stimulus
- RELATIVE REFRACTORY PERIOD: interval following the absolute refractory period in which a second action potential can be produced, but only if the stimulus strength is greater than usual because it needs to be able to activate the fewer Na+ channels that are available
ACTION POTENTIAL PROPAGATION:
- the production of local currents produced by an action potential, that trigger a new action potential at a site further along an axon
- action potential can only travel the length of a neuron if each point along the membrane is depolarized to its threshold
- the difference between potentials causes current to flow, and this local current depolarizes the adjacent membrane where it causes the voltage-gated Na+ channels located there to open; the current entering during an action potential is enough to depolarize the adjacent membrane to its threshold
- SEQUENTIAL OPENING AND CLOSING OF VOLTAGE-GATED NA+ AND K+ CHANNELS ALONG THE MEMBRANE TO SET OFF ACTION POTENTIALS
SALTATORY CONDUCTION:
- the regeneration of action potentials only at nodes of Ranvier along a myelinated axon
- ACTION potentials appear to jump from one node to the next as they propagate along a myelinated fiber (saltatory means to leap)
- faster than the propagation of unmyelinated fibers
- less charge leaks out of the myelinated sections
- charge is regenerated at the nodes of ranvier
GRITTY MECHANICS OF ACTION POTENTIAL MECHANISMS:
1. steady resting membrane potentials is near Ek, Pk>Pna, due to more open leak K+ channels than Na+ channels.
- local membrane is brought to threshold voltage by a depolarizing stimulus (like a neurotransmitter that binds to a ligand-gated ion channel) that opens and allows Na+ to enter the cell;
- Current through opening voltage-gated Na+ channels rapidly depolarizes the membrane, causing more Na+ channels to open; this creates a positive feedback loop; Na+ entry causes depolarization, which opens more voltage-gated Na+ channels and more depolarization, so on
- Inactivation of Na+ channels and delayed opening of voltage-gated K+ channels halt membrane depolarization; There is overshoot, so the membrane becomes positive on the inside and negative on the outside; soon, Na+ channels start to inactivate and K+ channels start to activate; this breaks the positive feedback loop
- Outward current through open voltage-gated K+ repolarizes the membrane back to a negative potential; the sluggish K+ channels repolarize the membrane to resting value
- Persistent current through slowly closing voltage-gated K+ channels hyperpolarizes membrane toward Ek; Na+ channels return from inactivated state to closed state (without opening); there is a period where the K+ permeability remains above resting potential and is hyperpolarized toward the K+ equilibrium; AFTERHYPERPOLARIZATION
- Closure of voltage-gated K+ channels returns the membrane potential to its resting value;
IN SUMMARY: whereas voltage-gated Na+ channels operate in a positive feedback mode at the beginning of an action potential, voltage-gated K+ channels bring the action potential to an end and induce their own closing through a negative feedback process
THINGS TO NOTE:
- the number of ions that cross the membrane during an action potential is incredibly tiny compared to the total number of ions in the cell
- not all membrane depolarizations in excitable cells trigger the positive feedback process that leads to an action potential; action potential only occurs when the initial stimulus plus the current through the Na+ channels it opens are sufficient enough to elevate the membrane potential beyond the threshold potential; ALL-OR-NONE CONCEPT
- there are drugs that block voltage-gated Na+ channels that prevent them from opening in response to depolarization (LOCAL ANESTHETICS LIKE NOVOCAINE AND LIDOCAINE) –> ACTION POTENTIAL CANNOT GIVE SENSATION OF PAIN;
- TETRODOTOXIN –> CAN LEAD TO DEATH, IN PUFFER FISH, NO NA+ COMPONENT OF ACTION POTENTIALS
***QUESTIONS: ask about mechanics of refractory periods? ask about membrane changes for potentials? saltatory?
6.8 Functional Anatomy of Synapses
BACKGROUND
SYNAPSES
- is an anatomically specialized junction between two neurons, at which the electrical activity in a presynaptic neuron influences the electrical activity of a postsynaptic neuron
- activity at synapses can increases or decrease the likelihood that the postsynaptic neuron will fire action potentials by producing a brief, graded potential in the postsynaptic membrane
- whether a postsynaptic cell fires an action potential depends on the number of synapses that are active and whether they are excitatory or inhibitory
- CONVERGENCE: the hundreds/thousands of synapses from many presynaptic cells that affect a single postsynaptic cell
- DIVERGENCE: a single presynaptic cell can send branches to affect many oter postsynaptic cells
EXCITATORY SYNAPSE: - brings the membrane of a postsynaptic cell closer to the threshold (depolarized) INHIBITORY SYNAPSE: - prevents a postsynaptic cell from approaching threshold by hyperpolarizing or stabilizing the membrane potential
ELECTRICAL SYNAPSES: - consist of gap junctions that allow current to flow between adjacent cells - plasma membranes joined by gap junctions - local currents resulting from arriving action potentials flow directly across the junction through the connecting channels, thus depolarizing the membrane of the second synapse - very rapid, but thought to be rare in adult mammals - current flows directly CHEMICAL SYNAPSES: - neurotransmitters stored in SYNAPTIC VESICLES are released by a presynaptic axon terminal into the synaptic cleft, where they transmit the signal from a presynaptic neuron to an adjacent postsynaptic neuron at a region called a postsynaptic density - typical chemical synapse structure - the axon of the presynaptic neuron ends in slight swellings, the axon terminals, which hold the SYNAPTIC VESCICLES that contain neurotransmitter molecules - the postsynaptic membrane adjacent to an axon terminal has a high density of membrane proteins that make up a specialized area cellaed the POSTSYNAPTIC DENSITY - A 10 NM TO 20 NM extracellular speace, the SYNAPTIC CLEFT, separates the presynaptic and postsynaptic neurons and prevents direct propagation of the current from the presynaptic neuron to the postsynaptic cell - THE MESSAGES ARE INSTEAD TRANSMITTED ACROSS THE SYNAPTIC CLEFT BY MEANS OF A CHEMICAL MESSENGER (NEUROTRANSMITTER) THAT IS RELEASED FROM THE PRESYNAPTIC AXON TERMINAL - COTRANSMITTER: more than one neurotransmitter released simultaneously from an axon
6.9 Mechanisms of Neurotransmitter Release
- depolarization of axon terminals opens voltage-gated Ca2+ channels in the membrane
- Ca2+ diffuses through channels down its electrochemical gradient into the cytosol of the terminal
- increased Ca2+ concentration causes cytosolic proteins SYNAPTOTAGMINS and SNAREs to induce vesicles ( docked at ACTIVE ZONES of a presynaptic neuron) containing neurotransmitters to fuse with the plasma membrane, thereby releasing neurotransmitters into the synaptic cleft
NITTY-GRITTY OF CHEMICAL SYNAPSE PROCESSES:
- action potential reaches terminal; depolarization during the action potential opens the Ca2+ channels; because the electrochemical gradient favors Ca2+ influx, Ca2+ flows into the axon terminal;
- voltage-gated Ca2+ channels open
- calcium enters axon terminal; Ca2+
ions activate processes that lead to the fusion of docked vesicles with synaptic terminal membrane; prior to this arrival, the vesicles are docked in the active zones by the interaction of a group of SNARE proteins (some in vesicle membrane, others in terminal) - neurotransmitter is released and diffuses into the cleft; Ca2+ ions enter during depolarization and then bind to a separate family of proteins associated with the vesicle called SYNAPTOTAGMINS, TRIGGERING A CONFORMATIONAL CHANGE IN THE SNARE COMPLEX THAT LEADS TO MEMBRANE FUSION AND NEUROTRANSMITTER RELEASE; 2 pathways from here: 1. vesicles fuse completely with membrane and are recycled later in endocytosis, 2. vesicles fuse briefly and release their contents and then reseal the pore and withdraw back into the axon terminal
- neurotransmitter binds to postsynaptic receptors;
- neurotransmitter removed from synaptic cleft
6.10 Activation of the Postsynaptic Cell
- postsynaptic cell neurotransmitter receptors may be IONOTROPIC, which contain an ion channel in their structure, or METABOTROPIC, which are linked with second-messenger systems and indirectly alter ion channels
a. the result of the binding of neurotransmitters to receptors is the opening or closing of specific ligand-gated ion channels in the postsynaptic plasma membrane which eventually leads to changes in the membrane potential in that neuron - the removal of neurotransmitters in the synaptic cleft causes the number of occupied receptors to decrease which returns the membrane to its resting state when the neurotransmitters are no longer bound
- excess neurotransmitters are removed from the synaptic cleft in order to terminate the signal and prevent diffusion out to other cells by:
a. REUPTAKE into the presynaptic cell for reuse; active transport
b. enzymatic degradation into inactive fragments; are inactive substances but some can be transported to presynaptic axon for reuse; enzymes for this process can be on the postsynaptic or presynaptic membrane or within the synaptic cleft
c. transport into glial cells; there they are degraded
d. diffuse away from the receptor site
TWO KINDS OF CHEMICAL SYNAPSES
- depends on the type of ion channel affected by the neurotransmitter once it binds to its receptor
EXCITATORY POSTSYNAPTIC POTENTIAL (EPSP):
- the electrical response in a postsynaptic cell at an excitatory chemical synapse is depolarization, bringing the membrane potential closer to threshold
a. usually opening nonselective channels that are permeable to Na+ and K+
b. net movement of ions into the postsynaptic cell is positive, slight depolarization
c. decreases in magnitude as it spreads away from the synapse by local current
d. only function is to membrane potential of postsynaptic neuron closer to threshold #
e. type of graded potential
- usually due to Na+ influx through nonspecific cation channels opening in postsynaptic cells
INHIBITORY POSTSYNAPTIC POTENTIAL (IPSP):
- hyperpolarizing graded potential generally or a stabilization
- activation lessens the likelihood that a postsynaptic cell will depolarize to threshold and generate an action potential
- either a hyperpolarization or a stabilization of the membrane potential at an inhibitory chemical synapse
- usually due to the opening of channels of Cl- or K+ in postsynaptic cell
a. Na+ permeability not affected
QUESTIONS: what does all of this membrane potential stuff mean here lol
6.11 Synaptic Integration
- action potentials are generally initiated by the temporal and spatial summation of many EPSPs
- action potentials can only be initiated by the combined effects of many EPSPs because single EPSP might be 0.5 mV when necessary is 15 mV to depolarize neural membrane to threshold
- thousands of synapses can occur on any one neuron, and hundred are active at a time
- the axon hillock has a more negative threshold than the membrane of the cell body or dendrites because it has a higher density of voltage-gated Na+ channels in that area of the membrane; this is why it is the first region to reach threshold whenever EPSPs summate and the resulting action potential is the propagated from this point down the axon
TEMPORAL SUMMATION
- summed potential created by more than one EPSP and/or IPSP arriving at a single synapse on a postsynaptic cell membrane in quick succession
- the potentials summate because an additional influx of positive ions occurs before ions leaking out through the membrane have returned it to the resting potential
SPATIAL SUMMATION
- summed potential created by more than one EPSP and/or IPSP arriving together at different synapses on a postsynaptic cell membrane
- two inputs occurred at different locations on the cells
- the interaction of multiple EPSPs through spatial and temporal summation can increase the inward flow of positive ions and bring the postsynaptic membrane to the threshold so that action potentials are initiated
6.12 Synaptic Strength
SYNAPTIC STRENGTH:
- effectiveness of a synapse; can be modified pre- and postsynaptically
PRESYNAPTIC MECHANICS
- neurotransmitter output of some presynaptic terminals is also altered by activation of membrane receptors on the terminals themselves
- activation of presynaptic receptors can influence Ca2+ influx into the terminal and thus the number of neurotransmitter vesicles that release neurotransmitter into the synaptic cleft
- AXO-AXONIC SYNAPSES are second synaptic endings that may be associated with a presynaptic receptor; they may have a direct influence on neuron A that affects the subsequent neuron indirectly; this is called PRESYNAPTIC INHIBITION/FACILITATION
PRESYNAPTIC INHIBITION:
- stimulatory action produced by an axon terminal of one neuron directly on the terminal of another; results in less neurotransmitter release
PRESYNAPTIC FACILITATION:
- stimulatory action produced by the axon terminal of one neuron directly on the terminal of another; results in more neurotransmitter release
AUTORECEPTORS
- some neurotransmitters are released by the axon terminal itself and act on it which allows a feedback mechanism to regulate its own neurotransmitter output
POSTSYNAPTIC MECHANISMS
- the ability of a given receptor to respond to it neurotransmitter can change
- postsynaptic alteration of synaptic strength may also occur, for example, due to receptor DESENSITIZATION; receptor responds normally when first exposed to the neurotransmitter but fails to respond in continued presence of neurotransmitter
- pathophysiology: certain medications and diseases may alter synaptic strength by numerous mechanisms, including neurotransmitter synthesis, secretion, degradation, or reuptake
- some toxins include: TETANUS TOXIN (destroys SNARE proteins so neurotransmitter release is inhibited and causes spastic paralysis), BOTULISM & BOTOX (stop muscle contractions0
- a drug might:
1. increase leakage of neurotransmitter from a vesicle to cytoplasm, exposing it to enzyme breakdown
2. increase transmitter release int cleft
3. block transmitter release
4. inhibit transmitter synthesis
5. block transmitter reuptake
6. block cleft or intracellular enzymes that metabolize transmitter
7. bind to receptor on presynaptic membrane to block (antagonist) or mimic (agonist) transmitter action
8. inhibit or stimulate second-messenger activity within postsynaptic cell
NITTY-GRITTY MECHANICS:
1. action potentials arriving at the presynaptic terminal cause voltage-gated Ca2+ ion channels to open
- Ca2+ ions diffuse into the cell and cause synaptic vesicles to release acetylcholine, a neurotransmitter molecule
- acetylcholine molecules diffuse from the presynaptic terminal across the synaptic cleft and bind to the receptor sites on the ligand-gated Na+ channels
- this causes the ligand-gated Na+ ion channels to open and Na+ ions diffuse into the postsynaptic cell making the membrane potential more positive
- if the membrane potential reaches threshold level, an action potential will be produced
6.13 Neurotransmitters and Neuromodulators
BACKGROUND
- in general, neurotransmitters cause EPSPs and IPSPs, and NEUROMODULATORS, (such as certain neuropeptides) cause, via second messengers, more complex metabolic effects in a postsynaptic cell
- the actions of neurotransmitters are usually faster than those of neuromodulators
- neuromodulators are often synthesized by the presynaptic cell and coreleased with the neurotransmitter
- neuromodulators are associated with slower events
- A compound that indirectly alters the effectiveness of a synapse by altering release of, or responsiveness to, a neurotransmitter.
- a substance can act as a neurotransmitter at one type of receptor and as a neuromodulator at another
a. receptors for neuromodulators often bring about changes in metabolic processes in neurons via G proteins coupled to second-messenger systems - major classes of neurotransmitters:
- ACETYLCHOLINE
> major neurotransmitter in the PNS at the neuromuscular junction (where motor neuron contacts a skeletal muscle cell)
> Neurons that release ACh are called CHOLINERGIC
> nicotinic receptors are present at neuromuscular junction and respond to both nicotine and ACh receptors; they one one of the subtypes of neurotransmitter receptors that normally binds to ACh
> Muscarinic ACh receptors- stimulated by muscarine at junctions where the PNS innervates peripheral glands, tissues, and organs like salivary glands, smooth muscle cells, and the heart
*Alzheimer’s degenerates neurotransmitter systems - BIOGENIC AMINES
> synthesized from amino acids (small charged molecules)
A. CATECHOLAMINES
> Dopamine (DA)- a monoamine neurotransmitter
> Norepinephrine (NE)- a catecholamine neurotransmitter involved in sympathetic regulation of smooth and cardiac muscle
> Epinephrine (Epi)
> some like MONOAMINE OXIDASE have drug inhibitors MOA inhibitors that increase the amount of norepinephrine and dopamine in a synapse by slowing their metabolic degradation and treat types of depression
B. SEROTONIN (5-hydroxytryptamine, 5-HT)
C. Histamine - AMINO ACIDS
> The most prevalent neurotransmitters in the CNS, where they affect virtually all neurons, are the amino acid neurotransmitters.
A. excitatory amino acids- ex: glutamate which has receptors AMPA and NMDA and is The primary neurotransmitter at an estimated 50% of excitatory synapses in the CNS
B. inhibitory amino acids- ex: (GABA or glycine)
4. NEUROPEPTIDES
> also act as neuromodulators; EX: ENDOGENOUS OPIOIDS (Eating and drinking behavior, Pain relief), oxytocin, tachykinins, Beta-endorphin, Enkephalins, Dynorphins
5. GASES including NITRIC OXIDE (gaseous neurotransmitter is produced from L-arginine by nitric oxide synthetase) and HYDROGEN SULFIDE- PURINES
> adenosine & ATP - LIPIDS
> prostaglandins
> endocannabinoids (Generated in response to Ca2+ entry into some postsynaptic cells, Include 2-arachidonoylglycerol, Receptors found in widespread locations throughout the CNS and PNS)
> leukotreines
> thromboxanes
- PURINES
- ACETYLCHOLINE
QUESTIONS: do we need to know the pathways for ACh?
6.14 Neuroeffector Communication
BACKGROUND
NEUROEFFECTOR JUNCTION:
- the synapse between a neuron and an effector cell
- the events at the neuroeffector junction (release of the neurotransmitter into extracellular space, diffusion of neurotransmitter to the effector cell, and binding with a receptor on the effector cell) are similar to those at synapses between neurons
- major neurotransmitters are ACh and norepinephrine
- receptors on the effector cells may be metabatropic or ionotropic
6.15 Central Nervous System: Brain
BACKGROUND
GENERAL CONCEPTS
- the brain consists of the FOREBRAIN (cerebrum, diencephalon), MIDBRAIN, and HINDBRAIN (pons, medulla oblongata, and cerebellum)
a. WHITE MATTER: primarily composed of myelinated axons traveling together in pathways called TRACTS
b. GRAY MATTER: composed primarily of cell bodies of neurons & unmyelinated fibers
- The cell bodies of neurons with similar functions are often clustered together to form nuclei in the CNS only
- A collection of neuron cell bodies within the central nervous system is properly referred to as a nucleus
CEREBRUM:
- made up of right and left cerebral hemispheres and several structure including
a. CEREBRAL CORTEX- outer shell of the cerebrum; composed of PARIETAL, FRONTAL, OCCIPITAL, and TEMPORAL LOBES; participates in conscious thought, memory, perception, learning, and generation of skilled movements; corpus callosum links the left and right cerebral hemispheres; The cerebral cortex is highly folded, even though it averages only 3 mm in thickness; groove= sulcus, ridges= girus
b. LIMBIC SYSTEM- SUBCORTICAL NUCLEI associated with learning and emotion
c. BASAL NUCLEI- subcortical nuclei involved with control of movement and posture
DIENCEPHALON:
- composed of:
a. THALAMUS (sensory relay; general arousal)
b. EPITHALAMUS (includes pineal gland; circadian rhythms)
c. HYPOTHALAMUS (controls many aspects of the internal environment, nervous and endocrine coordination)
CEREBELLUM:
- functions in posture, movement, and some kinds of memory
BRAINSTEM:
- composed of the midbrain, pons, and medulla oblongata; essential for life
a. contains RETICULAR FORMATION, which regulates arousal states, attention, control of heart and lung function, certain motor functions; runs throughout the core of the brainstem and consists of loosely arranged nuclei intermingled with bundles of axons. Its axons release biogenic amines that are critical in regulating sleep and wakefulness.
b. contain nuclei of the 10 of the 12 pairs of cranial nerves
DORSAL HORN VERSUS DORSAL ROOTS????
6.16 Central Nervous System: Spinal Cord
BACKGROUND
GENERAL INFORMATION
- axons of afferent and efferent neurons form the spinal nerves, carrying two-way information into and out of the CNS via structure called DORSAL and VENTRAL ROOTS
SPINAL CORD:
- together with the brain, comprises the CNS; lies within the VERTEBRAL COLUMN
a. central GRAY MATTER of spinal cord: contains cell bodies and dendrites
b. WHITE MATTER surrounds gray matter, contains myelinated axons that are organized into ascending or descending tracts
- Spinal nerves exiting between vertebrae of the spinal column contain axons of both afferent and efferent neurons
- cervical nerves
- thoracic nerves
- lumbar nerves
- sacral nerves
- coccygeal nerves
6.17 Peripheral Nervous System
BACKGROUND
PERIPHERAL NERVOUS SYSTEM (PNS):
- consists of 12 pairs of CRANIAL NERVES and 31 pairs of SPINAL NERVES) as well as neurons found in the gastrointestinal tract wall
a. most nerves contain both axons of both afferent and efferent neurons
AFFERENT DIVISION of the PNS:
- brings sensory information to the CNS
EFFERENT DIVISION of the PNS:
- divided into somatic and autonomic divisions
a. SOMATIC NERVOUS SYSTEM: sends MOTOR NEURONS that innervate skeletal muscle cells and release the neurotransmitter acetylcholine, causing contraction of muscle
> consists of a single neuron between the CNS and skeletal muscle cells
> innervates skeletal muscle cells (motor neurons innervate these)
> can lead only to muscle cell excitation
b. AUTONOMIC NERVOUS SYSTEM: innervates smooth muscle cells, gland cells, neurons of the intestinal tract, and others; can be excitatory or inhibitory
> has a two-neuron chain (connected by a synapse) between CNS and effector organ
> innervates smooth and cardiac muscle, glands, GI neurons, but not skeletal muscle cells
> can be either excitatory or inhibitory
