Calexcitin transformation of GABAergic synapses: From excitation filter to amplifier

Calexcitin transformation of GABAergic synapses: From excitation filter to amplifier

Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892

Communicated by Bernhard Witkop, National Institutes of Health, Bethesda, MD (received for review February 2, 1999)

Abstract

Encoding an experience into a lasting memory is thought to involve an altered operation of relevant synapses and a variety of other subcellular processes, including changed activity of specific proteins. Here, we report direct evidence that co-applying (associating) membrane depolarization of rat hippocampal CA1 pyramidal cells with intracellular microinjections of calexcitin (CE), a memory-related signaling protein, induces a long-term transformation of inhibitory postsynaptic potentials from basket interneurons (BAS) into excitatory postsynaptic potentials. This synaptic transformation changes the function of the synaptic inputs from excitation filter to amplifier, is accompanied by a shift of the reversal potential of BAS–CA1 postsynaptic potentials, and is blocked by inhibiting carbonic anhydrase or antagonizing ryanodine receptors. Effects in the opposite direction are produced when anti-CE antibody is introduced into the cells, whereas heat-inactivated CE and antibodies are ineffective. These data suggest that CE is actively involved in shaping BAS–CA1 synaptic plasticity and controlling information processing through the hippocampal networks.

Footnotes

↵ * To whom reprint requests should be addressed at: Laboratory of Adaptive Systems/NINDS/NIH, Building 36, Room 4A24, 36 Convent Dr., Bethesda, MD 20892. e-mail: mksun{at}codon.nih.gov.
ABBREVIATIONS:

ACET,

acetazolamide;

BAPTA,

1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid;

BAS,

basket neurons;

CA,

carbonic anhydrase;

CE,

calexcitin;

EPSPs,

excitatory postsynaptic potentials;

GABA,

γ-aminobutyrate;

IPSPs,

inhibitory postsynaptic potentials;

KYN,

kynurenate;

PSP,

postsynaptic potential;

RR,

ruthenium red;

RyR,

ryanodine receptors;

SCH,

Schaffer collateral pathway