Quantitative Analysis of Gaba and Glutamate Receptors in the Synapses of Hippocampal Interneurons

2 Summary Hippocampal glutamatergic pyramidal cells receive input from several types of GABA (gamma-amino-butyric acid)-releasing interneurons (IN-s) and innervate them reciprocally. Our goal was to characterise the receptor content that plays a role in the synaptic interactions of these neurons. Pyramidal cells expressing different GABA A receptors receive input on their axon initial segment from axo-axonic cells and on their soma from two kinds of basket cells, containing either parvalbumin (PV), or cholecystokinin (CCK). Using a quantitative electron microscopic immunogold technique, we proved that the synapses formed by the two types of basket cell show a difference in the subunit composition of GABA A receptors. We found that synapses made by PV positive basket cells showed five times less immunoreactivity for the α 2-subunit than synapses made PV negative (CCK positive) cells. This difference is due to specific GABA A receptor α-subunit composition, because neither synaptic size, nor total receptor content was different in these two synapse populations. Synapses established by axo-axonic cells showed an intermediate immunoreactivity but the highest density of the α 2-subunit in theier efferent synapses. Glutamatergic activation of IN-s involve N-methyl-D-aspartate (NMDA) type glutamate receptors expressed in type I synapses, mostly on their dendritic shafts. To compare the NMDA receptor content of synapses, we analysed four populations of synapse. Synapses i) on spines of pyramidal cells; ii) on PV positive IN dendritic shafts in str. radiatum; iii) on randomly found IN dendritic shafts in str. oriens and iv) on somatostatin-positive IN-al dendritic shafts and somata in str. oriens. The four populations of synapses significantly differed in labelling for the NR1 subunit; pyramidal cell spines having he highest and PV positive dendrites in str. radiatum the lowest immunoreactivity. In str. oriens, IN segments had a high variability of synaptic receptor content. These results show that synaptic GABA and glutamate receptor content is highly regulated in synapses established and received by hippocampal interneurons. Consequently, the synapse specific receptor expression contributes to the differential action of distinct interneurons and to the precise timing of network operations in the hippocampus. Introduction Hippocampal pyramidal cells receive GABAergic innervation from several distinct populations of interneurones [6]. Axo-axonic cells innervate only the axon initial segment (AIS), basket cells innervate mainly the soma, and other interneurones innervate only the dendrites. The basket cells express either parvalbumin (PV) or cholecystokinin [6]. These two neurochemically distinct types of basket cell differ in soma position, local and …