No abstract

Kaufman et al. imaged and optogenetically manipulated the activity of locus coeruleus axons to the mouse hippocampal area CA1 in vivo. They show that this projection is a key player in inducing hippocampal place cell reorganization during goal-directed spatial learning.

Environmental cues affect place cells responses, but whether this information is integrated versus segregated in distinct hippocampal cell populations is unclear. Here, we show that, in mice running on a treadmill enriched with visual-tactile landmarks, place cells are more strongly controlled by landmark-associated sensory inputs in deeper regions of CA1 pyramidal layer (CA1d). Many cells in CA1d display several firing fields correlated with landmarks, mapping positions slightly before or within the landmarks. Supporting direct involvement of sensory inputs, their firing fields show instantaneous responses to landmark manipulations, persist through change of context, and encode landmark identity and saliency. In contrast, cells located superficially in the pyramidal layer have single firing fields, are context specific and respond with slow dynamics to landmark manipulations. These findings suggest parallel and anatomically segregated circuits within CA1 pyramidal layer, with variable ties to landmarks, allowing flexible representation of spatial and non-spatial information.

The axon initial segment of hippocampal pyramidal cells is a key subcellular compartment for action potential generation, under GABAergic control by the ''chandelier'' or axo-axonic cells (AACs). Although AACs are the only cellular source of GABA targeting the initial segment, their in vivo activity patterns and influence over pyramidal cell dynamics are not well understood. We achieved cell-type-specific genetic access to AACs in mice and show that AACs in the hippocampal area CA1 are synchronously activated by episodes of locomotion or whisking during rest. Bidirectional intervention experiments in head-restrained mice performing a random foraging task revealed that AACs inhibit CA1 pyramidal cells, indicating that the effect of GABA on the initial segments in the hippocampus is inhibitory in vivo. Finally, optogenetic inhibition of AACs at specific track locations induced remapping of pyramidal cell place fields. These results demonstrate brain-state-specific dynamics of a critical inhibitory controller of cortical circuits.

Dendritic calcium signaling is central to neural plasticity mechanisms that allow animals to adapt to the environment. Intracellular calcium release (ICR) from the endoplasmic reticulum has long been thought to shape these mechanisms. However, ICR has not been investigated in mammalian neurons in vivo. We combined electroporation of single CA1 pyramidal neurons, simultaneous imaging of dendritic and somatic activity during spatial navigation, optogenetic place field induction, and acute genetic augmentation of ICR cytosolic impact to reveal that ICR supports the establishment of dendritic feature selectivity and shapes integrative properties determining output-level receptive fields. This role for ICR was more prominent in apical than in basal dendrites. Thus, ICR cooperates with circuit-level architecture in vivo to promote the emergence of behaviorally relevant plasticity in a compartment-specific manner.