Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus.
Nat Neurosci
; 14(4): 487-94, 2011 Apr.
Article
in En
| MEDLINE
| ID: mdl-21378974
ABSTRACT
The absence of the chloride channel CLC-3 in Clcn3(-/-) mice results in hippocampal degeneration with a distinct temporal-spatial sequence that resembles neuronal loss in temporal lobe epilepsy. We examined how the loss of CLC-3 might affect GABAergic synaptic transmission in the hippocampus. An electrophysiological study of synaptic function in hippocampal slices taken from Clcn3(-/-) mice before the onset of neurodegeneration revealed a substantial decrease in the amplitude and frequency of miniature inhibitory postsynaptic currents compared with those in wild-type slices. We found that CLC-3 colocalized with the vesicular GABA transporter VGAT in the CA1 region of the hippocampus. Acidification of inhibitory synaptic vesicles induced by Cl(-) showed a marked dependence on CLC-3 expression. The decrease in inhibitory transmission in Clcn3(-/-) mice suggests that the neurotransmitter loading of synaptic vesicles was reduced, which we attribute to defective vesicular acidification. Our observations extend the role of Cl(-) in inhibitory transmission from that of a postsynaptic permeant species to a presynaptic regulatory element.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Presynaptic Terminals
/
Chloride Channels
/
Synaptic Transmission
/
Gamma-Aminobutyric Acid
/
Hippocampus
/
Neural Inhibition
Limits:
Animals
Language:
En
Journal:
Nat Neurosci
Journal subject:
NEUROLOGIA
Year:
2011
Document type:
Article
Affiliation country:
United States