Johan Dahlin
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558 lines
6.8 KiB
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# Nervcellsfysiologi HT25.pdf
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**OCR Transcript**
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- Pages: 32
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- OCR Engine: pymupdf
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- Quality Score: 1.00
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---
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## Page 1
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Nervcellsfysiologi
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Textbooks:
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Bear kap:2-6
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Purves kap:2-8
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Block 1
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Nervcellsfysiologi
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Eric Hanse
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---
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## Page 2
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Action potentials ”in action”
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www.sciencemag.org SCIENCE VOL 338 5 OCTOBER 2012
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Functional cell assemblies,
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or engrams
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The withdrawal reflex
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---
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## Page 3
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Excitability
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– the likelihood of evoking action potentials
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-90
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-70
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+60
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Membrane
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potential (mV)
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10 ms
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Threshold
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0
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Excitation
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Inhibition
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---
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## Page 4
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Synaptic and Intrinsic Excitability
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Synaptic
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excitation
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+
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Intrinsic
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Excitation
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+
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Intrinsic
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inhibition
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Synaptic
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inhibtion
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Glutamate
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synapses
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GABA
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synapses
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Na channels
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Ca channels
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Extrasynaptic GluRs
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K channels
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Cl channels
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Extrasyn GABARs
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---
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## Page 5
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Modulation and Plasticity of Excitability
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Pl
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M d
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Pl
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M d
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Pl
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M d
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Pl
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M d
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Synap
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excitat
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Intrin
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Excitat
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Intrins
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inhibiti
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Synapt
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inhibtio
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Plasticity – based on neuronal activity - aims to create / erase engrams
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Modulation – based on realease of modulatory neurotransmitters –
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modulate the accessability of engrams
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---
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## Page 6
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Electrophysiology – different levels of reductionism
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Single protein
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Single synapse
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Single cell
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Cell assemblies
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Isolated cells
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Cell cultures
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Brain slices
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In vivo
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Patch-clamp recordings
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Extracellular recordings
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Network oscillations
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Brain organoids
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Optical recordings
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Multielectrode array
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recordings
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---
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## Page 7
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Membrane potential
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Na/K-pump &
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Transporters
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Equilibrium
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potentials
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Membrane
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potential
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Selective
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permeability
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Ion
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channels
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Concentration
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gradients
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---
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## Page 8
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Pumps, concentration differences and
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equilibrium potential
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Nernst equation
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Ejon = 2.303 (RT/zF) log([jon]u/[jon]i)
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Ejon = 61.54 log([jon]u/[jon]i)
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Ion concentrations in human cerebrospinal fluid and serum (in mM)
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Cerebrospinal fluid
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Serum
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Correlation
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K+
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2.9
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4.2
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No
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Na+
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147
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140
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Yes
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Cl-
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125
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100
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No
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Ca2+ Total
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1.2
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2.4
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Yes
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Ca2+ Free
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1.0
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1.2
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Mg2+ Total
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1.2
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0.8
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No
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Mg2+ Free
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1.0
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0.5
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Lyckenvik et al (2025) Brain Commun 24:fcaf201
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---
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## Page 9
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Ion channels
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Gating
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Selectivity
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Voltage
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Ligand
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Ca2+,
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cAMP,
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cGMP
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Temp
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Mech
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H+
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“leak”
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Na
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K
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N/K
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N/K/Ca
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Ca2+
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Cl/HCO3
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---
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## Page 10
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Leak channels
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Trends in Pharmacological Sciences (2008) 29:11
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The resting permeability
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for K+ is much higher
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than for Na+, but the
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driving force (at resting
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membrane potential) is
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much higher for Na+ than
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for K+. The resultant
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currents for K+ and Na+
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are therefore equal
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---
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## Page 11
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Membrane potential
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-90
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-70
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+60
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Vm (mV)
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10 ms
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Threshold
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0
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Excitation
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Inhibition
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EK
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ECl
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ENa
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Depol
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Hyperpol
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RMP
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Glu
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GABA
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Vm = 61.54 mV log
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PK [K+]u + PNa[Na+]u
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PK [K+]i + PNa[Na+]i
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The Goldman equation
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Repol
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---
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## Page 12
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Action potential – ”all-or-none”
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---
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## Page 13
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Propagation of the action potential
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Myelin
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Diameter
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Temperatur
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---
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## Page 14
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Extracellular recording of action potentials
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---
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## Page 15
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Refractory period following the action
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potential
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Absolute refractory period = Voltage-gated Na+-channels
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are inactivated, making a new action potential impossible.
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Relative refractory period = Voltage-gated Na+-channels de-
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inactivates during this period and the membrane potential is
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hyperpolarized. A stronger than normal depol is required to
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evoke an action potential.
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---
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## Page 16
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Optical recording of the action potential
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Hochbaum et al (2014) All-optical electrophysiology in mammalian neurons using
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engineered microbial rhodopsins Nature Methods 11: 825-833
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---
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## Page 17
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Synaptic excitation and inhibition
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Synaptic
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excitation
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+
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Synaptic
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inhibtion
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AMPAR
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NMDAR
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Excitatory synapse
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”Modulatory Rec”
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Inhibitory synapse
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(GABA)
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”Modulatory Rec”
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GABAAR
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GABABR
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---
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## Page 18
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Glu and GABA synapses
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Input →
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Output →
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Cortical pyramidal cell:
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ca. 30000 Glutamate synapses (90%)
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ca. 2000 GABA synapses (10%)
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Megías, Emri, Freund & Gulyás (2001) Neuroscience 102:527
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Kasthuri et al (2015) Saturated reconstruction of a
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volume of neocortex Cell 162: 648661
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1 µm
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---
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## Page 19
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Presynaptic release of transmitter vesicle
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SNARE-mediated exocytosis
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---
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## Page 20
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Glutamate uptake in astrocytes
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---
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## Page 21
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Synapses are usually small and unreliable, but
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many (and plastic)
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3 quantal parameters determine the signalling
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strength of a synaptic connection
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Synaptic strength = n x p x q
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n = no. of release sites
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p = release probability
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The probability that an action potential will cause the release of one vesicle
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q = quantal size
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The magnitude of the postsynaptic response to one vesicle
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2 ms
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10 pA
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Recording from one synapse
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1 µm
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---
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## Page 22
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1. The AMPA receptor channel:
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-opened by glutamate
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-permeates Na+ and K+
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-gives rise to a brief (ca. 10 ms) EPSP
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2. The NMDA receptor channel:
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-opened by glutamate (and Gly/D-Ser) + depol
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-permeates Na+, K+ and Ca2+
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- gives rise to a brief long-lasting (ca. 100 ms) EPSP
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-is necessary for the induction of synaptic plasticity; Long-
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term potentiation (LTP) och long-term depression (LTD).
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3. Metabotropic glutamate receptors (mGluRs) are G-
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protein coupled receptors that, for example, can give rise
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to Ca2+ release from ER and facilitate synaptic plasticity.
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The Glutamate synapse
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---
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## Page 23
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The GABA synapse
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GABAA Rec
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GABAB Rec
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---
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## Page 24
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The i.c. Cl- concentration determines the
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response of the GABAA receptor channels
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---
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## Page 25
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Intrinsic
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Excitation
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+
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Intrinsic
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inhibition
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Intrinsic excitability – all ion channels of the neuron,
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except the ligand-gated in the synapses
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From Hille ”Ion channels in excitable membranes”
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E.c. Calcium
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---
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## Page 26
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Families of voltage-gated Na+, Ca2+ and K+
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channels
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Voltage-gated K-channels
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Neuron, Volume 85, Issue 2, 2015, 238 - 256
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---
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## Page 27
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Regulation of action potential frequency –
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AfterHyperPolarisation (AHP) and gKca2+
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Nicoll, RA
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---
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## Page 28
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Different firing patterns because of differences
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in intrinsic excitability
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---
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## Page 29
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Modulation and Plasticity of Excitability
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Pla
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Modu
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Pla
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Modu
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Pla
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Modu
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Pla
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Modu
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Synaptic
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excitation
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+
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Intrinsic
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Excitation
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+
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Intrinsic
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inhibition
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Synaptic
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inhibtion
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---
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## Page 30
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Neuromodulation
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Co-transmitters
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”Classical”
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ACh, NA, 5-HT,
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Histamin, DA
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Co-transmitters
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Peptides
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Orexin, Galanin,
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Endorphin, CCK, VIP,
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Oxytocin…
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Retrograde
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transmitters
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endocannabinoids,
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NO, neurotrophins
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Hormones
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Cortisol, Estrogen,
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Progersteron,
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Ghrelin, Insulin
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Vasopressin, AF…
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Gliotransmitters
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Glu
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ATP → Adenosine
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D-serine, Taurine
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Lactate
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Neurotransmitters
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Glu via mGluRs
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GABA via GABABRs
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Cytokines, Chemokines
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TNFα
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IL-1β….
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Modulate:
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*Release probability
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*Intrinsic excitability
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*Plasticity
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---
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## Page 31
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Modulation and Plasticity of Excitability
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Pla
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Modu
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Pla
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Modu
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Pla
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Modu
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Pla
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Modu
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Synaptic
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excitation
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+
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Intrinsic
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Excitation
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+
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Intrinsic
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inhibition
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Synaptic
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inhibtion
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---
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## Page 32
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Long-term synaptic plasticity (min – years); LTP
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and LTD
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---
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