Cell type- and input-specific differences in the number and subtypes of synaptic GABA(A) receptors in the hippocampus.
Networks of parvalbumin (PV)-expressing basket cells are implicated in synchronizing cortical neurons at various frequencies, through GABA(A) receptor-mediated synaptic action. These cells are interconnected by GABAergic synapses and gap junctions, and converge with a different class of cholecystokinin-expressing, PV-negative basket cells onto pyramidal cells. To define the molecular specializations in the synapses of the two basket cell populations, we used quantitative electron microscopic immunogold localization of GABA(A) receptors. Synapses formed by PV-positive basket cells on the somata of pyramidal cells had several-fold higher density of alpha1 subunit-containing receptors than synapses made by PV-negative basket cells, most of which were immunonegative. The density of the beta2/3 subunits was similar in the two populations of synapse, indicating similar overall receptor density. Synapses interconnecting parvalbumin-expressing basket cells contained a 3.6 times higher overall density of GABA(A) receptor (beta2/3 subunits) and 3.2 times higher density of alpha1 subunit labeling compared with synapses formed by boutons of PV-positive basket cells on pyramidal cells. Thus, PV-positive basket cells mainly act through alpha1 subunit-containing GABA(A) receptors, but the receptor density depends on the postsynaptic cell type. These observations, together with previously reported enrichment of the alpha2 subunit-containing receptors in synapses made by PV-negative basket cells, indicate that the number and subtypes of GABA(A) receptors present in different synapse populations are regulated by both presynaptic and postsynaptic influences. The high number of GABA(A) receptors in synapses on basket cells might contribute to the precisely timed phasing of basket cell activity.
Klausberger
Thomas
T
Medical Research Council, Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford University, Oxford OX1 3TH, United Kingdom. thomas.klausberger@pharm.ox.ac.uk
Roberts
J David B
JD
Somogyi
Peter
P
D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D021122:Protein Subunits; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000145:classification* / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D021122:Protein Subunits; D011963:Receptors, GABA-A