Single Bursts of Individual Granule Cells Functionally Rearrange Feedforward Inhibition

Abstract

The sparse single-spike activity of dentate gyrus granule cells (DG GCs) is punctuated by occasional brief bursts of 3–7 action potentials. It is well-known that such presynaptic bursts in individual mossy fibers (MFs; axons of granule cells) are often able to discharge postsynaptic CA3 pyramidal cells due to powerful short-term facilitation. However, what happens in the CA3 network after the passage of a brief MF burst, before the arrival of the next burst or solitary spike, is not understood. Because MFs innervate significantly more CA3 interneurons than pyramidal cells, we focused on unitary MF responses in identified interneurons in the seconds-long postburst period, using paired recordings in rat hippocampal slices. Single bursts as short as 5 spikes in <30 ms in individual presynaptic MFs caused a sustained, large increase (tripling) in the amplitude of the unitary MF-EPSCs for several seconds in ivy, axo-axonic/chandelier and basket interneurons. The postburst unitary MF-EPSCs in these feedforward interneurons reached amplitudes that were even larger than the MF-EPSCs during the bursts in the same cells. In contrast, no comparable postburst enhancement of MF-EPSCs could be observed in pyramidal cells or nonfeedforward interneurons. The robust postburst increase in MF-EPSCs in feedforward interneurons was associated with significant shortening of the unitary synaptic delay and large downstream increases in disynaptic IPSCs in pyramidal cells. These results reveal a new cell type-specific plasticity that enables even solitary brief bursts in single GCs to powerfully enhance inhibition at the DG-CA3 interface in the seconds-long time-scales of interburst intervals.SIGNIFICANCE STATEMENT The hippocampal formation is a brain region that plays key roles in spatial navigation and learning and memory. The first stage of information processing occurs in the dentate gyrus, where principal cells are remarkably quiet, discharging low-frequency single action potentials interspersed with occasional brief bursts of spikes. Such bursts, in particular, have attracted a lot of attention because they appear to be critical for efficient coding, storage, and recall of information. We show that single bursts of a few spikes in individual granule cells result in seconds-long potentiation of excitatory inputs to downstream interneurons. Thus, while it has been known that bursts powerfully discharge (“detonate”) hippocampal excitatory cells, this study clarifies that they also regulate inhibition during the interburst intervals.

Dentate gyrus population activity during immobility supports formation of precise memories

“…For instance, the fraction of CA1 neurons recruited during sharp wave ripple mediated replay of behaviourally relevant sequences [23][24][25][26][27][28][29][30] is much higher than the recruitment of GCs in network events. One consequence of the sparseness of network events is that they are predicted to recruit highly constrained CA3 ensembles, both because of the sparse excitatory connectivity of mossy fibers in CA3, and because of the properties of the powerful inhibitory circuits in the CA3 region [31][32][33] . This has been suggested to be important in the capability to store information in CA3, while conserving the pattern separation benefits of the dentate gyrus 34,35 .…”

Slow‐decaying presynaptic calcium dynamics gate long‐lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse

“…This scenario would be consistent with a recently discovered phenomenon at the granule cell to CA3 interneurons synapses. At MF to CA3 interneuron synapses, the passage of an AP burst in granule cells induces a novel form of long‐lasting facilitation in the CA3 inhibitory network (Neubrandt et al., 2018). More precisely, a short burst of granule cell firing specifically maintains MF to interneuron synapses in a state of elevated release probability over several seconds, which will cause an enhanced recruitment of interneuron in response to subsequent granule cell firing (Neubrandt et al., 2018).…”

Quantitative firing pattern phenotyping of hippocampal neuron types

“…Moreover, single burst of action potentials in CA3 axons (Schaffer collaterals) can induce robust and stable long-term potentiation at synapses on CA1 pyramidal neurons, provided that the postsynaptic depolarization triggers a dendritic spike 79 . Recent results have also revealed that single bursts in DG granule cells may selectively alter specific functional components of the downstream circuit, such as feedforward inhibitory interneurons 80 .…”