I. Basics

I. Basics

Electrophysiology is the study of cell electrical

activity resulting from ion channel function.

Electrolyte composition of the cell

Na+: 5-10 mMK+: 110-145 mMCa2+: 100 nMCl-: 5-50 mM

Na+: 145 mMK+: 5-10 mMCa2+: 2 mMCl-

: 145 mM

OUT ION CHANNELS

Voltage-gated Ligand-gated

} Glu, Ach

♦ GABA

IN

Fundamental laws

Nernst's equation: Er = RT/F ln [Co/Ci]

Driving force = Em - Er

Ohm's law: V = R x I

A simplified view of cell-cell communication

Ligand-gated channels code for input

……...….

Neurotransmitter(s)

VG channels

Voltage-gated channels code for output

Baseline

Na leak

GABAA IPSPs

GABAB IPSP

Baseline

Subthreshold AMPA EPSP

Threshold AMPA EPSP

NMDA EPSP

NMDA + GABAA PSPs

II. MethodsSystems level (106+cells)

- EEG, evoked potentials

Nuclear (ensemble) level (102-103+ cells)- Population spike

Single-unit (extracellular) recording (1-3 cells)- In vivo microiontophoresis

Cell level- Intracellular recording- Patch-clamp (whole-cell recording)

Subcellular level- Patch-clamp (single-channel recording)

Cellular electrophysiology

Selective antagonism of GABA responses in the cuneate nucleus of the

anesthetized rat

Configurations of the patch-clamp technique

Configurations of the patch-clamp technique

Patch-clamp dates

⟨ 1976: First patch-clamp recording (first time ion channels wereobserved!)Neher and Sakmann, Nature 260:799

⟨ 1981: Comprehensive account of patch-clamp methods publishedHamill et al., Pflügers Arch 391:85

⟨ 1989: Methods for patch-clamp in slices publishedEdwards et al., Pflügers Arch 414:600

⟨ 1991: Nobel prize awarded to Neher and Sakmann⟨ 1993: Infra-red differential interference contrast (IR-DIC) methods

publishedStuart et al., Pflügers Arch 423:511

The voltage-clamp technique

III. From channels to behavior

The thalamocortical augmented response (AR)

Circuits involved in the AR

Cellular mechanism of the AR

Behavioral component of the AR