Similar GABAA receptor subunit composition in somatic and axon initial segment synapses of hippocampal pyramidal cells

Abstract

Hippocampal pyramidal cells (PCs) express many GABAAR subunit types and receive GABAergic inputs from distinct interneurons. Previous experiments revealed input-specific differences in α1 and α2 subunit densities in perisomatic synapses, suggesting distinct IPSC decay kinetics. However, IPSC decays evoked by axo-axonic, parvalbumin- or cholecystokinin-expressing basket cells were found to be similar. Using replica immunogold labeling, here we show that all CA1 PC somatic and AIS synapses contain the α1, α2, β1, β2, β3 and γ2 subunits. In CA3 PCs, 90% of the perisomatic synapses are immunopositive for the α1 subunit and all synapses are positive for the remaining five subunits. Somatic synapses form unimodal distributions based on their immunoreactivity for these subunits. The α2 subunit densities in somatic synapses facing Cav2.1 (i.e. parvalbumin) or Cav2.2 (cholecystokinin) positive presynaptic active zones are comparable. We conclude that perisomatic synapses made by three distinct interneuron types have similar GABAA receptor subunit content.DOI: http://dx.doi.org/10.7554/eLife.18426.001

Potentiating α2 subunit containing perisomatic GABAA receptors protects against seizures in a mouse model of Dravet syndrome

“…This is consistent with previous reports demonstrating that α 1 containing receptors are functionally localized to distal dendritic synapses whereas α 2 containing GABA A receptors preferentially mediate perisomatic phasic inhibition (Prenosil et al 2006). Using high resolution EM freeze fracture immunolabelling, it was recently demonstrated that synapses on the soma and axon initial segment (AIS) contain receptors with both α 1 and α 2 subunits (Kerti-Szigeti & Nusser, 2016). Moreover, prior work had suggested a remarkable input specific molecular segregation of GABA A receptor subunits.…”

“…Rather distinct synapses onto the soma and AIS from PV and CCK interneurons have similar subunit compositions where both α 1 and α 2 subunits are present in most labelled synapses (Kasugai et al . ; Kerti‐Szigeti & Nusser, ). Our functional results using the selective pharmacological profile of AZD7325 are consistent with inhibitory synapses localized close to the soma containing receptors with the α 2 subunit.…”

“…). Using high resolution EM freeze fracture immunolabelling, it was recently demonstrated that synapses on the soma and axon initial segment (AIS) contain receptors with both α 1 and α 2 subunits (Kerti‐Szigeti & Nusser, ). Moreover, prior work had suggested a remarkable input specific molecular segregation of GABA A receptor subunits.…”

Methionine Sulfoxide Reductase-B3 (MsrB3) Protein Associates with Synaptic Vesicles and its Expression Changes in the Hippocampi of Alzheimer’s Disease Patients

“…4) it is likely that the MsrB3-ir CA1 pyramidal somatic puncta associate with somatic synapses. CA1 pyramidal neurons have somatic synapses with presynaptic zones belonging to inhibitory interneurons [20]. Somatic inhibitory synapses in CA1 pyramidal neurons are characterized by the excitatory activity-related rapid structural plasticity resulting in synapse enlargement and increased efficiency of somatic inhibition[21].…”

Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia

“…Both the α1 and α2 subunits are found in GABAA receptors in the AIS (51, 52). In addition, in layers 2–3 of monkey PFC the expression of GABAA α1 mRNA increases and that of α2 decreases across postnatal development (53).…”