Age-related alterations of GABAergic input to CA1 Pyramidal neurons and its control by nicotinic acetylcholine receptors in rat hippocampus

The aim of this study was to determine whether age-associated alterations in the GABAergic input to pyramidal neurons in the hippocampus are due to a dysfunction of GABAergic interneurons, and/or a decrease in their cholinergic control via nicotinic receptors (nAChRs). Electrophysiological recording...

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Bibliographic Details
Published in:Neuroscience 2006-09, Vol.142 (1), p.187-201
Main Authors: Potier, B., Jouvenceau, A., Epelbaum, J., Dutar, P.
Format: Article
Language:English
Subjects:
Age Factors
aging
Aging - physiology
Alkaloids - pharmacology
Analysis of Variance
Animals
Azocines - pharmacology
Bicuculline - pharmacology
Calbindins
cytisine
donepezil
Dose-Response Relationship, Radiation
Drug Interactions
Electric Stimulation - methods
electrophysiology
Excitatory Amino Acid Antagonists - pharmacology
GABA Antagonists - pharmacology
gamma-Aminobutyric Acid - metabolism
Hippocampus - cytology
Immunohistochemistry - methods
Inhibitory Postsynaptic Potentials - drug effects
Inhibitory Postsynaptic Potentials - physiology
Inhibitory Postsynaptic Potentials - radiation effects
inhibitory synaptic transmission
Nicotinic Antagonists - pharmacology
Parvalbumins - metabolism
Patch-Clamp Techniques
Pyramidal Cells - drug effects
Pyramidal Cells - physiology
Pyramidal Cells - radiation effects
Quinolizines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Nicotinic - physiology
S100 Calcium Binding Protein G - metabolism
Somatostatin - metabolism
Vesicular Acetylcholine Transport Proteins - metabolism
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Summary:The aim of this study was to determine whether age-associated alterations in the GABAergic input to pyramidal neurons in the hippocampus are due to a dysfunction of GABAergic interneurons, and/or a decrease in their cholinergic control via nicotinic receptors (nAChRs). Electrophysiological recordings were obtained from pyramidal cells in the CA1 area of hippocampal slices from young (3–4 months old) and aged (25–30 months old) Sprague–Dawley rats. Synaptic GABA A receptor-mediated inhibitory postsynaptic currents and inhibitory postsynaptic potentials induced by stimulation of the stratum oriens were significantly smaller in aged rats. The frequency (but not amplitude) of spontaneous and miniature GABA inhibitory postsynaptic currents (IPSCs) was reduced in aged rats, suggesting a presynaptic alteration. Tetanic stimulation of cholinergic afferents to release endogenous acetylcholine, or an exogenous application of the nAChR agonist cytisine, increased the frequency of spontaneous IPSCs in young rats; however these effects were not evident in aged rats, indicating that the nicotinic control of GABA release is lowered during aging. None of these age-related alterations were reversed by a chronic treatment with donepezil, a cholinesterase inhibitor. Immunofluorescent labeling of GABA interneurons with somatostatin (SOM), parvalbumin (PV) or calbindin (CB), together with the vesicular acetylcholine transporter VAChT, revealed a selective loss of subpopulations of SOM and CB positive interneurons. This loss was associated with a general decrease in density of the cholinergic network in aged rats. Thus, the lower GABAergic inhibition observed in the aged rat hippocampus is due to a selective loss/dysfunction of subpopulations of GABAergic interneurons, associated with a widespread cholinergic deficit.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2006.06.040