Age‐dependent remodelling of inhibitory synapses onto hippocampal CA1 oriens‐lacunosum moleculare interneurons

• Published in: The Journal of physiology Vol. 589; no. 20; pp. 4885 - 4901
• Main Authors: Salesse, Charleen, Mueller, Christopher Lacharité, Chamberland, Simon, Topolnik, Lisa
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 15.10.2011; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Age; Age Factors; Animals; CA1 Region, Hippocampal - physiology; Female; In Vitro Techniques; Inhibitory Postsynaptic Potentials - physiology; Interneurons - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuroscience: Cellular/Molecular; Patch-Clamp Techniques; Receptors, GABA-A - deficiency; Receptors, GABA-A - genetics; Receptors, GABA-A - physiology; Rodents; Synapses - physiology
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/jphysiol.2011.215244

Non‐Technical Summary  The main function of the inhibitory synapse is to provide the membrane hyperpolarization and, thereby, to control the level of activity of its target cell. Extensively studied in pyramidal neurons, the properties of inhibitory synapses that target inhibitory interneurons remain largely unknown. We studied the properties of inhibitory synapses formed onto interneurons involved in the hippocampal feedback inhibitory circuit. Our data revealed a significant, age‐dependent strengthening of inhibition of interneurons due to the synaptic incorporation of the α5 subunit of the GABAA receptor. This novel mechanism of age‐dependent refinement of local circuit inhibition may have a direct impact on the hippocampal network activity and performance during development.   Stratum oriens‐lacunosum moleculare interneurons (O‐LM INs) represent the major element of the hippocampal feedback inhibitory circuit, which provides inhibition to the distal dendritic sites of CA1 pyramidal neurons. Although the intrinsic conductance profile and the properties of glutamatergic transmission to O‐LM INs have become a subject of intense investigation, far less is known about the properties of the inhibitory synapses formed onto these cells. Here, we used whole‐cell patch‐clamp recordings in acute mouse hippocampal slices to study the properties and plasticity of GABAergic inhibitory synapses onto O‐LM INs. Surprisingly, we found that the kinetics of inhibitory postsynaptic currents (IPSCs) were slower in mature synapses (P26–40) due to the synaptic incorporation of the α5 subunit of the GABAA receptor (a5‐GABAAR). Moreover, this age‐dependent synaptic expression of a5‐GABAARs was directly associated with the emergence of long‐term potentiation at IN inhibitory synapses. Finally, the slower time course of IPSCs observed in O‐LM INs of mature animals had a profound effect on IN excitability by significantly delaying its spike firing. Our data suggest that GABAergic synapses onto O‐LM INs undergo significant modifications during postnatal maturation. The developmental switch in IPSC properties and plasticity is controlled by the synaptic incorporation of the a5‐GABAAR subunit and may represent a potential mechanism for the age‐dependent modifications in the inhibitory control of the hippocampal feedback inhibitory circuit.