ENVIRONMENTAL ENRICHMENT FINE-TUNES INHIBITORY CIRCUIT DYNAMICS AND DENDRITIC PROCESSING IN HIPPOCAMPAL CA1 CIRCUITS

Environmental enrichment (EE) enhances hippocampal excitatory synaptic transmission and facilitates hippocampus-dependent learning and memory. It is well established that dendritic inhibition mediated by somatostatin (SOM)-expressing interneurons via α5-containing GABA_A receptors (α5-GABA_AR) plays a key role in modulating NMDAR-dependent firing and dendritic integration in CA1 pyramidal neurons. While EE-induced changes in excitatory hippocampal circuits have been widely studied, it remains unclear whether inhibitory networks undergo similar experience-dependent remodelling.
Here, we investigated how EE shapes inhibitory synaptic transmission in the hippocampal CA1 region. Using whole-cell patch-clamp recordings in acute hippocampal slices from C57BL/6 mice (7-11 weeks old), we assessed electrically evoked and miniature synaptic activity in animals housed under standard conditions (STD) or EE for 2-3 weeks. All experiments were approved by the Basel Cantonal Veterinary Office.
EE enhanced excitatory synaptic transmission onto CA1 pyramidal neurons via increase in the number of excitatory synapses and evoked AMPAR- and NMDAR-mediated currents. In parallel, EE increased the number of inhibitory synaptic inputs onto CA1 pyramidal neurons. Further recordings revealed that EE enhanced evoked dendrite-targeting inhibition onto CA1 pyramidal neurons. Moreover, EE significantly decreased inhibitory synaptic transmission onto dendrite-targeting SOM-interneurons. Lastly, EE increased the functional contribution of α5-GABA_AR to dendritic inhibition, identifying a receptor-specific mechanism that might modulate dendritic excitability in CA1 pyramidal neurons.
Together, these findings suggest that EE shifts CA1 circuit dynamics towards enhanced α5-GABA_AR-mediated dendritic inhibition. This experience-dependent remodelling of inhibitory circuits is likely to fine-tune dendritic synaptic integration and plasticity during periods of enhanced brain activity associated with EE.