Cell Type-Specific Long-Term Plasticity at Glutamatergic Synapses onto Hippocampal Interneurons Expressing either Parvalbumin or CB₁Cannabinoid Receptor

Abstract

Different GABAergic interneuron types have specific roles in hippocampal function, and anatomical as well as physiological features vary greatly between interneuron classes. Long-term plasticity of interneurons has mostly been studied in unidentified GABAergic cells and is known to be very heterogeneous. Here we tested whether cell type-specific plasticity properties in distinct GABAergic interneuron types might underlie this heterogeneity. We show that long-term potentiation (LTP) and –depression (LTD), two common forms of synaptic plasticity, are expressed in a highly cell type-specific manner at glutamatergic synapses onto hippocampal GABAergic neurons. Both LTP and LTD are generated in interneurons expressing parvalbumin (PV+), whereas interneurons with similar axon distributions but expressing cannabinoid receptor-1 (CB1R+) show no lasting plasticity in response to the same protocol. In addition, LTP or LTD occurs in PV+ interneurons with different efferent target domains. Perisomatic-targeting PV+ basket and axo-axonic interneurons express LTP, whereas glutamatergic synapses onto PV+ bistratified cells display LTD. Both LTP and LTD are pathway-specific, independent of NMDARs and occur at synapses with calcium-permeable AMPA receptors. Plasticity in interneurons with CP-AMPARs strongly modulates disynaptic GABAergic transmission onto CA1 pyramidal cells. We propose that long-term plasticity adjusts the synaptic strength between pyramidal cells and interneurons in a cell type-specific manner and in the defined CA1 interneurons shifts the spatial pattern of inhibitory weight from pyramidal cell dendrites to the perisomatic region.

Contextual learning requires synaptic AMPA receptor delivery in the hippocampus

“…*P < 0.001 vs. MPR-AA; into synapses at inhibitory interneurons. In fact, parvalbuminpositive interneurons provide many GluR1-positive synapses (35) and display high inward rectification of AMPAR-current (36). Although it is not clear if learning induces synaptic delivery of AMPARs at GABAergic interneurons, learning-dependent increase in GABA release in the CA1 area (37) may be caused by the increase in excitatory inputs to interneurons.…”

A Specific Class of Interneuron Mediates Inhibitory Plasticity in the Lateral Amygdala

“…This rise in postsynaptic calcium does not require activation of NMDARs or release from intracellular stores. However, it is blocked when tetanic stimulation is delivered in the presence of the AMPA/kainate receptor antagonist kynurenic acid indicating that, as in several types of interneurons in the hippocampus, LTP is initiated by calcium influx through calcium-permeable AMPA receptors (Lei and McBain, 2002;Kullmann and Lamsa, 2007;Oren et al, 2009;Nissen et al, 2010).…”

Cell Type-Specific Expression of Acid-Sensing Ion Channels in Hippocampal Interneurons

“…Interestingly, our results demonstrate that ASIC2 subunit mRNAs were not detected in most BCs and relatively small ASIC currents were detected in BC dendrites. Thus, subunit composition of ASICs in different types of GABAergic inhibitory interneurons might also contribute to cell type-specific long-term plasticity at glutamatergic synapses onto hippocampal interneurons (Nissen et al, 2010).…”