UC San Diego

In order to form a memory, transient experiences are captured by neurons in the brain and transformed into long-lasting changes in cell circuitry and connectivity. To elucidate the mechanisms underlying memory formation it is necessary to determine how pyramidal neuron (PN) activity is transformed into changes in the future output of the neuron. NPAS4, an immediate early gene that is expressed transiently following PN activity, has been linked to changes in inhibitory synaptic connectivity. Specifically, NPAS4 leads to recruitment of somatic CCK basket cell synapses and destabilization of CCK dendritic inhibitory synapses. This cell-autonomous regulation of inhibitory synapses indicates that NPAS4 plays a role in shaping CA1 PN activity in vivo but, to date, there are no studies investigating this. Here we use an optotagging approach to compare the in vivo activity of simultaneously recorded, intermingled, NPAS4 wild type and knockout (KO) CA1 PNs from freely moving mice. We find that NPAS4 KO neurons have impaired spatial tuning and that this is accompanied by deficits in the stability of their firing across the session. Furthermore, NPAS4 KO neurons are less bursty within the place field. This reduction in bursting has implications for other aspects of spike timing including theta-coupling and phase precession. Specifically, we find that NPAS4 KO neurons are less theta-coupled within the place field and that their phase precession slopes are more shallow. Taken together our results demonstrate that NPAS4, through the reorganization of inhibitory synapses, is important for both the tuning of place fields in CA1 and for the refinement of sequences.