Local Potentials_Slides.pdf

Local Potentials Your handout is a transcript of this lecture 1 Local potentials initiate APs • Local potentials are graded phenomena – result from opening/closing of ion-permeable channels – amplitudes/duration vary – have longer duration than APs, permit them to sum • in time: temporal summatio...

Local Potentials Your handout is a transcript of this lecture 1 Local potentials initiate APs • Local potentials are graded phenomena – result from opening/closing of ion-permeable channels – amplitudes/duration vary – have longer duration than APs, permit them to sum • in time: temporal summation • with distance: spatial summation • Three general types of local potentials – synaptic potentials in neurons – endplate potentials in skeletal-muscle cells – generator (or receptor potentials) in neurons associated with sensory receptors 2 Synaptic potentials in neurons • Presynaptic axons branch forming – axon collaterals – contact postsynaptic-neuron soma or dendrites at synapses 3 Postsynaptic potentials at synapses • If they depolarize postsynaptic cell… – called excitatory postsynaptic potentials (EPSPs) – tend to elicit APs in postsynaptic cell • If they hyperpolarize (or stabilize) PD in postsynaptic cell… – called inhibitory postsynaptic potentials (IPSPs) – tend to inhibit production of APs in postsynaptic cell 4 Ionic basis for EPSPs and IPSPs • Presynaptic AP  opening of postsynaptic channels • …at an excitatory synapse (EPSP), – roughly equally permeable to Na+ and K+ (gNa = 1.3 gK) – gK alone would hyperpolarize cell, but coupled with gNa  depolarization in direction toward 15 mV (well above threshold) • …at an inhibitory synapse (IPSP), – permeable to K+ and/or Cl – gK hyperpolarizes cell – gCl usually produces no change in potential • Why? Hint: what is typical value for ECl? 5 Soma acts as integrator • EPSPs and IPSPs typically small events (< 5 mV): a single one rarely alters ability of neuron to fire AP • 1000’s of synapses on soma and dendrites: – soma acts as integrator – sums up effects of all EPSPs and IPSPs occurring at any given time • How is it done? …by summing the effects of the EPSPand IPSP-induced electrotonic currents – soma non-excitable: lacks rapidly activating Na+ channels: cannot fire AP – first place AP can be generated: initial segment (axon hillock) of axon 6 Membrane PD at hillock • Monitor Vm with microelectrode at hillock – synapses at two points: A (close to hillock) and B (far away from hillock) 7 Assume: synapses A and B are excitatory • While measuring Vm at hillock, stimulate presynaptic neurons individually, then together: A B A+B 5 mV 10 m sec • “A” causes a larger EPSP (4-mV) than “B” (2-mV). Why? – “A” is closer to hillock than “B”: much of B’s electrotonic current exits soma before reaching hillock • “A+B” larger depolarization: spatial summation, but… – individual potentials do not sum up algebraically! 8 Repetitive stimulation of a single synapse • Duration of EPSPs much longer than AP, so a second AP can arrive at synapse before a previous EPSP has decayed to zero: A A A A A A 5 mV 10 msec • Larger depolarizations resulting from temporal summation – Again… peak depolarizations do not sum algebraically – Increasing frequency leads to still larger depolarizations 9 Summation can lead to AP at hillock • …whenever it leads to a depolarization to threshold: Why is figure poorly drawn? Hint: AP duration • Above: temporal summation (repetitive stimulation at one synapse). Same could be achieved with spatial summation (simultaneous stimulation of multiple presynaptic neurons) 10 IPSPs can cancel effects of EPSPs • Referring to previous diagram with two synapses: assume “A” is excitatory and “B” is inhibitory... A B A+B 5 mV 10 msec • “B” produces hyperpol. IPSP (due to gK and/or gCl) • “A+B” attenuates EPSP (spatial summation), but… – amplitudes do not sum algebraically (as before) 11 Silent IPSPs resulting from gCl • …can produce no change in Vm, yet still effective in countering EPSP • Example: assume the following… – – – – Equilibrium PDs: Resting g’s: EPSP g increase: IPSP g increase: ENa = +50 mV, EK = 100 mV, ECl = 75 mV gK = 100 nS, gNa = 20 nS, gCl = 0 nS gK = 10 nS, gNa = 10 nS gCl = 20 nS • Recall: equation for Vm... g K E K  g Na E Na  gCl ECl Vm  gT 12 Resulting membrane potentials C ondition g N a (nS) g K (nS) g C l (nS) R esting 20 100 0 EPSP 20+10 = 100+10 = 0 30 110 IPSP 20 100 0+20 = 20 EPSP + 20+10 = 100+10 = 0+20 = IPSP 30 110 20 V m (m V ) 75.0 67.9 75.0 68.8 • IPSP alone: no change in Vm (silent IPSP) • EPSP alone: 7.1-mV depolarization • IPSP + EPSP: 6.2-mV depolarization (spatial summation) 13 Summation of EPSPs and IPSP... • Individual potentials DO NOT sum up! • Sum up the increases in conductances, then use membranepotential equation to determine resulting potential. • Typical IPSPs are hyperpolarizing potentials, but some can actually be depolarizing potentials – How so? ...if ECl is less negative than Vrest – Still effective in countering effects of EPSPs! 14 Importance of neural inhibition • Roughly half of all neural synapses are inhibitory (generate IPSPs) – activity of presynaptic inhibitory synapses   activity of postsynaptic neurons • ADHD (attention-deficit hyperactivity disorder) – Treated with drugs (amphetamines, Ritalin®) that neural activity (specific brain centers) – activity  inhibition of brain motor centers   motor (muscle) activity (reducing hyperkinesis) 15 Tetanus (the disease) • Infection by Clostridia tetani – Anaerobic spore-forming bacterium – Lives in soil, ubiquitous worldwide – Oral ingestion: spores do not germinate – Inject via puncture wound: spores germinate, bugs release neurotoxin (“tetanus toxin”) • Tetanus toxin irreversibly blocks inhibitory synapses – on soma/dendrites of -motor neurons (spinal cord) – loss of inhibition  muscle contraction (“lockjaw,” progressing to face and trunk)  death by asphyxiation • No effective treatment! Prevent with immunization (booster every 10 years) 16 Endplate potentials (EPPs) • Endplate = region of membrane in skeletal-muscle fibers where motor neuron innervates muscle fiber at the neuromuscular junction (NMJ): axon collaterals of motor neuron spreading over endplate 17 EPPs are depolarizing potentials • Like EPSPs, result from gNa and gK – much larger depolarization than EPSP due to large area of endplate membrane – single EPP always sufficient to elicit an AP in muscle fiber • endplate located adjacent to membrane containing rapidly activating Na+ channels • AP in muscle fiber triggers contraction • No inhibitory EPPs! – Inhibition of muscle contraction occurs at neural synapses (c.f., tetanus) 18 Generator (or receptor) potentials • Detection of physical stimuli via sensory receptors – E.g., pressure (touch) receptor, temp. receptor, etc. – Associated with afferent neuron • Carries information toward central nervous system – Sensory info. always transduced to trains of APs • AP frequency encodes amplitude, e.g., 10 spikes/sec for light touch, 100 spikes/sec for heavy touch • Local potential that generates trains of APs is termed a generator (or receptor) potential 19 Well studied receptor: Pacinian corpuscle • A pressure (touch) receptor found in palms, fingers, and other regions: multilamellar membrane structure (like layers of an onion) myelinated axon corpuscle with multilamellar structure removed 20 Corpuscle has stretch-sensitive ion channels • Unmyelinated naked axon (region A): – Few fast-activating Na+ channels – Non-excitable (cannot generate APs) • Depress naked-axon region – opens stretch-sensitive channels causing inward current and depolarized receptor potential – local electrotonic current flows down inside of axon – depolarizes first node (labeled B), and if threshold reached, elicits AP that propagates down axon – maintain pressure: second AP generated after refractory periods of first 21 Receptor potential is graded • Amount of depolarization proportional to intensity of pressure • In comparison with a small pressure: – Larger pressure larger depolarization  larger electrotonic current  threshold at node reached earlier in relative refractory period  next AP generated sooner  higher frequency of APs • Important concept: – Each AP arriving in central nervous system has same amplitude – Number of APs per second (frequency) encodes the stimulus intensity (called frequency encoding) 22