Biology subjects

Bischofberger, J.

Publications and source records attributed to Bischofberger, J..

4 recordsLinked to original sources

bioRxiv2026

Enrichment experience improves hippocampal sparse coding via inhibitory circuit plasticity

Environmental enrichment enhances hippocampus-dependent learning and memory, yet the underlying circuit mechanisms remain largely unknown. Here we combined miniscope calcium imaging during spatial exploration with synaptic circuit analysis in hippocampal slices to determine how enrichment experience alters hippocampal network dynamics. Prolonged enrichment reduced average firing rates and immediate early gene expression in CA1 pyramidal cells, while increasing peak firing and spatial selectivity. Population activity was sparser and more diverse, resulting in a higher Gini index. Circuit analysis revealed enhanced excitatory drive onto both pyramidal cells and somatostatin (SOM) interneurons, together with a strengthened SOM-mediated feedback inhibition onto pyramidal cells. Suppressing SOM interneurons occluded the enrichment-induced augmentation of sparsity and Gini index and prevented improvements in hippocampus-dependent learning. These findings demonstrate that environmental enrichment dynamically enhances hippocampal sparse coding through potentiation of SOM-mediated feedback inhibition, linking experience-dependent inhibitory plasticity to enhanced memory performance.

neuroscience↗

bioRxiv2026

A single dose of the antipsychotic drug clozapine has long-term behavioral and functional effects in mice

Antipsychotic dosing regimens, commonly daily or via slow-release compounds, are designed to maintain steady-state plasma concentrations. They are guided by their plasma half-life that is typically in the range of several hours. This schedule contrasts with the slow time course of therapeutic efficacy, which often takes weeks to develop fully. This discrepancy led us to hypothesize that the effects of a single dose of an antipsychotic drug might be detectable well beyond the time window predicted by receptor occupancy. To test this, we administered a single dose of the antipsychotic drug clozapine to mice. We observed long-term behavioral effects and changes to cortical activity patterns up to several days after administration. Specifically, clozapine induced a decorrelation of activity in the dorsal cortex observable up to 9 days post administration. This effect was driven by a genetically and functionally distinct subset of layer 5 intratelencephalic neurons, possibly through a clozapine induced increase in the reliability of long-range inhibitory functional influence that exhibited a similar long-term change. Thus, our findings suggest that longer dosing intervals for antipsychotic drugs warrant clinical exploration.

neuroscience↗

bioRxiv2022

Trans-cellular control of synapse properties by a cell type-specific splicing regulator

The recognition of synaptic partners and specification of synaptic properties are fundamental for the function of neuronal circuits. Terminal selector transcription factors coordinate the expression of terminal gene batteries that specify cell type-specific properties. Moreover, pan-neuronal alternative splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell type-specific loss-of-function studies to uncover the contribution of the nuclear RNA binding protein SLM2 to hippocampal synapse specification. Focusing on hippocampal pyramidal cells and SST-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins, thereby generating cell type-specific isoforms. In the absence of SLM2, cell type-specification, differentiation, and viability are unaltered and neuronal populations exhibit normal intrinsic properties. By contrast, cell type-specific loss of SLM2 results in highly selective, non-cell autonomous synaptic phenotypes, altered synaptic transmission, and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner.

neuroscience↗

bioRxiv2020

Sparsification of AP firing in adult-born hippocampal granule cells via voltage-dependent α5-GABAA receptors

GABA can depolarize immature neurons close to the action potential (AP) threshold in development and adult neurogenesis. Nevertheless, GABAergic synapses effectively inhibit AP firing in newborn granule cells of the adult hippocampus as early as 2 weeks post mitosis. The underlying mechanisms are largely unclear. Here we analyzed GABAergic inputs in newborn 2- to 4-week-old hippocampal granule cells mediated by soma-targeting parvalbumin (PV) and dendrite-targeting somatostatin (SOM) interneurons. Surprisingly, both interneuron subtypes activate 5-subunit containing GABAA receptors (5-GABAARs) in young neurons, showing a nonlinear voltage dependence with increasing conductance around the AP threshold. By contrast, in mature cells, PV interneurons mediate linear GABAergic synaptic currents lacking 5-subunits, while SOM-interneurons continue to target nonlinear 5-GABAARs. Computational modelling shows that the voltage-dependent amplification of 5-GABAAR opening in young neurons is crucial for inhibition of AP firing to generate balanced and sparse firing activity, even with depolarized GABA reversal potentials.

neuroscience↗