Highlights d Functionally distinct neuronal ensembles exist within a single memory engram d Fosand Npas4-dependent ensembles undergo distinct synaptic modifications after CFC d Fosand Npas4-dependent ensembles drive memoryguided behaviors in opposite directions d Memory generalization and discrimination, respectively, require MEC and CCK + interneurons
Connecting neural circuit output to behaviour can be facilitated by precise chemical manipulation of specific cell populations 1,2. Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways 3,4. Their application to studies of behaviour has thus far been hampered by a trade-off between low temporal resolution of systemic injection versus invasiveness of implanted cannulas or infusion pumps 2. Here, we develop remotely controlled chemomagnetic modulation-a nanomaterials-based technique that permits pharmacological interrogation of targeted neural populations in freely moving subjects. The heat Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Understanding the function of nitric oxide (NO), a lipophilic messenger in physiological processes across nervous, cardiovascular and immune systems, is currently impeded by the dearth of tools to deliver this gaseous molecule
in situ
to specific cells. To address this need, we developed iron sulfide nanoclusters that catalyse NO generation from benign sodium nitrite in the presence of modest electric fields. Locally generated NO activates the NO-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and latency of TRPV1-mediated Ca
2+
responses can be controlled by varying the applied voltage. Integrating these electrocatalytic nanoclusters with multimaterial fibres allows NO-mediated neuronal interrogation
in vivo
.
In situ
generation of NO within the ventral tegmental area via the electrocatalytic fibres evoked neuronal excitation in the targeted brain region and its excitatory projections. This NO generation platform may advance mechanistic studies of the role of NO in the nervous system and other organs.
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