Cellular neurophysiology

Norbert Hájos

Institute of Experimental Medicine

Hungarian Academy of Sciences
1. Ionic composition of nerve cells
2. Action potential generation
3. Presynaptic site of neurotransmission
4. Postsynaptic site of neurotransmission
5. Retrograde signaling
6. Short- and long-term synaptic plasticity
Ionic composition of nerve cells
For K+ ~ -80 mV
For Na+ ~ +80 mV
For Cl- ~ -65 mV
Resting membrane potential
Maintaining the ion concentration through the nerve cell membrane
Action potential
 The Nobel Prize in Physiology for
Medicine 1963

“for their discoveries concerning the ionic mechanisms

Sir J. C. A. L. A.F. involved in excitation and inhibition in the peripheral
Eccles Hodgkin Huxley and central portions of the nerve cell membrane"

Ion movements during action potentials

http://pb010.anes.ucla.edu/
Determining of ion movements during AP

A. L. A.F.
Hodgkin Huxley
Determining of ion movements during AP
 The Nobel Prize in Physiology for
Medicine 1991
"for their discoveries concerning the function of single ion
channels in cells"
Erwin Neher Bert Sakmann Patch-clamp recordings

Ion channel
Direct investigation of the properties of ion channels
Ion movements
during action
potential
Structure and function of voltage-gated ion channels
Diverse types of
action potentials
in the nervous
system
AP propagation
Dendrite
Soma

Axon
initial
Axon segment
Amplitude of backpropagating action potentials depends on the pattern

Stuart & Sakmann, 1995

Williams & Stuart, 1999

Remove of K+ from the extracellular space
Synaptic transmission

The presynaptic site

The mechanisms of neurotransmission
Structure of synaptic junctions
Chemical nature of
neurotransmission

Otto Loewi
(1920)
 Synaptic vesicles and the associated proteins

The Nobel Prize in Physiology for

Medicine in 2013
„for their discoveries of machinery regulating vesicle trafficing,
a major transport system in our cells”
Release of neurotransmitter molecules from vesicles
Synaptic transmission

The postsynaptic site

The mechanisms of neurotransmission
Sturcture of the postsynaptic site
The structure of ionotropic and metabotropic receptors
 Fast transmission (10ms) - ionotropic

Excitatory: Inhibitory:
glutamate receptors- AMPA r. (Na+ és K+) GABA receptors - GABAa r. (Cl-)
kainate r. (Na+ és K+) glycine receptors (Cl-)
NMDA r. (Na+ , K+ és Ca2+)
acetylcholine receptors-nicotinic r. (Na+ , K+ és Ca2+)
serotonergic receptors- 5HT3 r. (Na+ , K+ és Ca2+)

Slow transmission (100ms) -metabotropic

glutamate receptors- mGluR r. (mGluR1-8)
GABA receptors - GABAb r.
acetylcholine receptors-muscarinic r. (M1-5)
serotonergic receptors- 5HT1-8
dopaminergic receptors- D1-D6
adrenergic receptors- alpha1,2; beta1,2
Histamine receptors - H1-3
Excitatory neurotransmission
(eg. glutamate or acetylcholine r.)
Inhibitory neurotransmission
(pl. GABAa receptors)
 Midbrain
cholinergic
cells
Basal forebrain

Raphe nuclei
Locus coeruleus

Ventral
tegmental
area
Molecular logic of second messengers
Retrograde signaling

i) Gaseous molecules: nitrogen monoxide (NO), carbonmonoxide (CO)

ii) Peptides: BDNF, dynorfine

iii) Lipids: endocannabinoids, arachidonyl acid

iv) Classical neurotranszmitters: GABA, glutamate

 Retrograde signaling
Action potential train

Inhibitory postsynaptic potentials- IPSP

Wilson and Nicoll, Science, 2002

CB1
Short-term plasticity at synapses

Target-selectivity!

Depressing, facilitating, steady in time

Reasons for depression: i) Large release probability
ii) De-sensitisation of postsynaptic receptors
iii) intracellular factors (eg. spermine)

Reasons for facilitation: Accummulation of Ca2+ in the presynaptic boutons

Controlled by presynaptic receptors!

 Building blocks of cortical networks

PC B M

Reyes et al., 1998

Routing of information transfer by short-term plasticity

Pouille & Scanziani, 2004

Long-term plasticity at synapses

Target selectivity!

LTP – long-term potenciation

LTD – long-term depression

Induction protocols: i) high-frequency stimulation of fibers (Bliss & Lomo, 1973)

ii) spike timing-dependent plasticity

Mechanisms: NMDA-dependent, non-NMDA dependent, receptor

insertion, replacing receptor subunits, retrograde signaling...
 Spike time-dependent plasticity - STDP

Markram et al., 1997

Direct activation of astrocytes (by depolarisation or Ca2+ uncaging)
enhances GABA release via kainate receptors

Kang et al., 1998