Biology subjects

Grienberger, C.

Publications and source records attributed to Grienberger, C..

5 recordsLinked to original sources

bioRxiv2026

Subicular Plateaus Signal Reward Locations during Goal-Directed Behavior

The hippocampus is essential for spatial learning, yet how its principal output structure, the subiculum, encodes behaviorally relevant information during navigation remains poorly understood. Because subicular neurons exhibit prominent burst firing, elucidating how this bursting is generated during behavior is critical. Using in vivo whole-cell recordings from dorsal subiculum neurons in head-fixed mice performing a goal-directed navigation task, we show that many bursts correspond to plateau events consisting of a series of action potentials riding on a large ([~]20-30 mV) sustained subthreshold depolarization. Subicular plateaus were synaptic in origin and required NMDA receptor activation. Organizing plateaus by the membrane potential preceding their onset revealed distinct behavioral associations. Plateaus initiated from relatively hyperpolarized membrane potentials preferentially clustered near reward locations, whereas plateaus initiated from more depolarized membrane potentials were more spatially distributed and showed weaker reward specificity. Reward-related clustering required a fixed, learned reward location and dynamically rearranged during learning of a new reward location. Together, our findings identify subicular plateaus as a prominent cellular substrate of hippocampal bursting output and demonstrate that intracellular membrane potential state organizes the behavioral associations of subicular plateaus during goal-directed learning.

neuroscience↗

bioRxiv2025

Dendrite-targeting OLM interneurons regulate the formation of learning-related CA1 place cell representations

Spatial learning depends on hippocampal CA1 place cell representations, which form rapidly through behavioral timescale synaptic plasticity (BTSP). BTSP is driven by dendritic plateau potentials proposed to arise from the interaction of an excitatory target signal from entorhinal cortex layer 3 (EC3) and inhibitory feedback reflecting the current CA1 population state. However, the cellular source of this feedback has remained unknown. Using two-photon Ca2+ imaging in mice during spatial learning, we found that dendrite-targeting oriens-lacunosum moleculare (OLM) interneurons increased their activity at behaviorally salient locations in a manner consistent with previously described environment-specific CA1 representations and EC3 target signals. Causal manipulations revealed that silencing a genetically defined subset of OLM interneurons late in learning enhanced BTSP and place field formation, whereas activating them early suppressed place field formation. These findings identify OLM interneurons as a key inhibitory feedback element regulating BTSP and the formation of hippocampal representations during learning.

neuroscience↗

bioRxiv2025

An unsuspected physiological role for mGluRIII glutamate receptors in hippocampal area CA1

Group III metabotropic glutamate receptors (mGluRIII) are expressed broadly throughout the neocortex and hippocampus but are thought to inhibit neurotransmitter release only at a subset of synapses and in a target cell- specific manner. Accordingly, previous slice physiology experiments in hippocampal area CA1 showed that mGluRIII receptors inhibit glutamate and GABA release only at excitatory and inhibitory synapses formed onto GABAergic interneurons, not onto pyramidal cells. Here, we show that the supposed target cell-specific modulation of GABA release only occurs when the extracellular calcium concentration in the recording solution is higher than its physiological concentration in the cerebrospinal fluid. Under more physiological conditions, mGluRIII receptors inhibit GABA release at synapses formed onto both interneurons and pyramidal cells but limit glutamate release only onto interneurons. This previously unrecognized form of mGluRIII-dependent, pre-synaptic modulation of inhibition onto pyramidal cells is accounted for by a reduction in the size of the readily releasable pool, mediated by protein kinase A and its vesicle-associated target proteins, synapsins. Using in vivo whole-cell recordings in behaving mice, we demonstrate that blocking mGluRIII activation in the intact CA1 network results in net effects consistent with decreased inhibition and significantly alters CA1 place cell activity. Together, these findings challenge our current understanding of the role of mGluRIII receptors in the control of synaptic transmission and encoding of spatial information in the hippocampus.

neuroscience↗

bioRxiv2021

Entorhinal cortex directs learning-related changes in CA1 representations

Learning-related changes in brain activity are thought to underlie adaptive behaviors1,2. For instance, the learning of a reward site by rodents requires the development of an over-representation of that location in the hippocampus3-6. However, how this learning-related change occurs remains unknown. Here we recorded hippocampal CA1 population activity as mice learned a reward location on a linear treadmill. Physiological and pharmacological evidence suggests that the adaptive over-representation required behavioral timescale synaptic plasticity (BTSP)7. BTSP is known to be driven by dendritic voltage signals that we hypothesized were initiated by input from entorhinal cortex layer 3 (EC3). Accordingly, the CA1 over-representation was largely removed by optogenetic inhibition of EC3 activity. Recordings from EC3 neurons revealed an activity pattern that could provide an instructive signal directing BTSP to generate the over-representation. Consistent with this function, exposure to a second environment possessing a prominent reward-predictive cue resulted in both EC3 activity and CA1 place field density that were more elevated at the cue than the reward. These data indicate that learning-related changes in the hippocampus are produced by synaptic plasticity directed by an instructive signal from the EC3 that appears to be specifically adapted to the behaviorally relevant features of the environment.

neuroscience↗

bioRxiv2020

Bidirectional synaptic plasticity rapidly modifies hippocampal representations independent of correlated activity

Learning requires neural adaptations thought to be mediated by activity-dependent synaptic plasticity. A relatively non-standard form of synaptic plasticity driven by dendritic plateau potentials has been reported to underlie place field formation in hippocampal CA1 neurons. Here we found that this behavioral timescale synaptic plasticity (BTSP) can also reshape existing place fields via bidirectional synaptic weight changes that depend on the temporal proximity of plateau potentials to pre-existing place fields. When evoked near an existing place field, plateau potentials induced less synaptic potentiation and more depression, suggesting BTSP might depend inversely on postsynaptic activation. However, manipulations of place cell membrane potential and computational modeling indicated that this anti-correlation actually results from a dependence on current synaptic weight such that weak inputs potentiate and strong inputs depress. A network model implementing this bidirectional synaptic learning rule suggested that BTSP enables population activity, rather than pairwise neuronal correlations, to drive neural adaptations to experience.

neuroscience↗