Calcium permeable AMPA receptor-dependent long lasting plasticity of intrinsic excitability in fast spiking interneurons of the dentate gyrus decreases inhibition in the granule cell layer

Abstract

The local fast-spiking interneurons (FSINs) are considered to be crucial for the generation, maintenance, and modulation of neuronal network oscillations especially in the gamma frequency band. Gamma frequency oscillations have been associated with different aspects of behavior. But the prolonged effects of gamma frequency synaptic activity on the FSINs remain elusive. Using whole cell current clamp patch recordings, we observed a sustained decrease of intrinsic excitability in the FSINs of the dentate gyrus (DG) following repetitive stimulations of the mossy fibers at 30 Hz (gamma bursts). Surprisingly, the granule cells (GCs) did not express intrinsic plastic changes upon similar synaptic excitation of their apical dendritic inputs. Interestingly, pairing the gamma bursts with membrane hyperpolarization accentuated the plasticity in FSINs following the induction protocol, while the plasticity attenuated following gamma bursts paired with membrane depolarization. Paired pulse ratio measurement of the synaptic responses did not show significant changes during the experiments. However, the induction protocols were accompanied with postsynaptic calcium rise in FSINs. Interestingly, the maximum and the minimum increase occurred during gamma bursts with membrane hyperpolarization and depolarization respectively. Including a selective blocker of calcium-permeable AMPA receptors (CP-AMPARs) in the bath; significantly attenuated the calcium rise and blocked the membrane potential dependence of the calcium rise in the FSINs, suggesting their involvement in the observed phenomenon. Chelation of intracellular calcium, blocking HCN channel conductance or blocking CP-AMPARs during the experiment forbade the long lasting expression of the plasticity. Simultaneous dual patch recordings from FSINs and synaptically connected putative GCs confirmed the decreased inhibition in the GCs accompanying the decreased intrinsic excitability in the FSINs. Experimentally constrained network simulations using NEURON predicted increased spiking in the GC owing to decreased input resistance in the FSIN. We hypothesize that the selective plasticity in the FSINs induced by local network activity may serve to increase information throughput into the downstream hippocampal subfields besides providing neuroprotection to the FSINs.

Hippocampal GABAergic interneurons and memory

“…A similar mGluR5-dependent IE in DG PV neurons was observed after the induction of bursts of synaptic stimulation of the mossy fiber pathway at gamma frequency. 145 These two studies demonstrate a clear link between inhibitory IE and memory-related oscillations. IE has also been found in hippocampal SOM cells.…”

The contribution of ion channels in input-output plasticity

“…Thus, Er81 level is high in weakly active circuits (corresponding to high levels of Kv1.1 channels) whereas it is low in highly active circuits (corresponding to low levels of Kv1.1 channels). Reduced input resistance has also been reported in fast-spiking interneurons from the dentate gyrus following synaptic stimulations of the mossy-fibers (Dasgupta & Sikdar, 2015). This modulation is mediated by HCN channels and depends on activation of calcium-permeable AMPA receptor.…”

Quantitative properties of a feedback circuit predict frequency-dependent pattern separation

“…The DG is thought to subserve this task by converting different types of inputs to sparse, nonoverlapping activity patterns of granule cells (GCs). However, in contrast to the insect olfactory system, the DG feedback circuit is extremely complex, comprising numerous interconnected interneuron types (Supplementary Table 1) [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] . For instance, interneurons subserving feedback inhibition are also incorporated into circuits mediating feedforward inhibition 32,35,40 and disinhibition 21,29 .…”