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1.
Cell ; 186(3): 543-559.e19, 2023 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-36669484

RESUMEN

Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging with targeted optogenetic activation and silencing of pre- and post-synaptic neurons to study the mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, targeted optogenetic activation of individual CA1 cells at specific places induced stable representations of these places in the targeted cells. Optical elicitation, recording, and modulation of synaptic transmission in behaving mice revealed that activity in presynaptic CA2/3 cells was required for the induction of plasticity in CA1 and, furthermore, that during induction of these place fields in single CA1 cells, synaptic input from CA2/3 onto these same cells was potentiated. These results reveal synaptic implementation of hippocampal behavioral timescale plasticity and define a methodology to resolve synaptic plasticity during learning and memory in behaving mammals.


Asunto(s)
Región CA1 Hipocampal , Hipocampo , Ratones , Animales , Región CA1 Hipocampal/fisiología , Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Aprendizaje/fisiología , Neuronas , Transmisión Sináptica/fisiología , Mamíferos
2.
Nature ; 615(7951): 292-299, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36859543

RESUMEN

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1-3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3-8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.


Asunto(s)
Conducta Animal , Encéfalo , Emociones , Corazón , Animales , Ratones , Ansiedad/fisiopatología , Encéfalo/fisiología , Mapeo Encefálico , Emociones/fisiología , Corazón/fisiología , Conducta Animal/fisiología , Electrofisiología , Optogenética , Corteza Insular/fisiología , Frecuencia Cardíaca , Channelrhodopsins , Taquicardia/fisiopatología , Marcapaso Artificial
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