RESUMEN
Investigators conducting behavioral experiments often need precise control over the timing of the delivery of stimuli to subjects and to collect the precise times of the subsequent behavioral responses. Furthermore, investigators want fine-tuned control over how various multi-modal cues are presented. behaviorMate takes an "Intranet of Things" approach, using a networked system of hardware and software components for achieving these goals. The system outputs a file with integrated timestamp-event pairs that investigators can then format and process using their own analysis pipelines. We present an overview of the electronic components and GUI application that make up behaviorMate as well as mechanical designs for compatible experimental rigs to provide the reader with the ability to set up their own system. A wide variety of paradigms are supported, including goal-oriented learning, random foraging, and context switching. We demonstrate behaviorMate's utility and reliability with a range of use cases from several published studies and benchmark tests. Finally, we present experimental validation demonstrating different modalities of hippocampal place field studies. Both treadmill with burlap belt and virtual reality with running wheel paradigms were performed to confirm the efficacy and flexibility of the approach. Previous solutions rely on proprietary systems that may have large upfront costs or present frameworks that require customized software to be developed. behaviorMate uses open-source software and a flexible configuration system to mitigate both concerns. behaviorMate has a proven record for head-fixed imaging experiments and could be easily adopted for task control in a variety of experimental situations.
RESUMEN
The hippocampus is a multi-stage neural circuit that is critical for memory formation. Its distinct anatomy has long inspired theories that rely on local interactions between neurons within each subregion in order to perform serial operations important for memory encoding and storage. These local computations have received less attention in CA1 area, the primary output node of the hippocampus, where excitatory neurons are thought to be only very sparsely interconnected. However, recent findings have demonstrated the power of local circuitry in CA1, with evidence for strong functional interactions among excitatory neurons, regulation by diverse inhibitory microcircuits, and novel plasticity rules that can profoundly reshape the hippocampal ensemble code. Here we review how these properties expand the dynamical repertoire of CA1 beyond the confines of feedforward processing, and what implications they have for hippocampo-cortical functions in memory formation.
Asunto(s)
Región CA1 Hipocampal , Navegación Espacial , Región CA1 Hipocampal/fisiología , Hipocampo/fisiología , Memoria/fisiología , Neuronas/fisiologíaRESUMEN
Neurons in the hippocampus exhibit a striking selectivity for specific combinations of sensory features, forming representations that are thought to subserve episodic memory. Even during completely novel experiences, hippocampal "place cells" are rapidly configured such that the population sparsely encodes visited locations, stabilizing within minutes of the first exposure to a new environment. What mechanisms enable this fast encoding of experience? Using virtual reality and neural population recordings in mice, we dissected the effects of novelty and experience on the dynamics of place field formation. During place field formation, many CA1 neurons immediately modulated the amplitude of their activity and shifted the location of their field, rapid changes in tuning predicted by behavioral timescale synaptic plasticity (BTSP). Signatures of BTSP were particularly enriched during the exploration of a novel context and decayed with experience. Our data suggest that novelty modulates the effective learning rate in CA1, favoring rapid mechanisms of field formation to encode a new experience.
Asunto(s)
Hipocampo , Células de Lugar , Animales , Región CA1 Hipocampal/fisiología , Hipocampo/fisiología , Aprendizaje/fisiología , Ratones , Plasticidad Neuronal/fisiología , Neuronas/fisiologíaRESUMEN
The hippocampus plays a critical role in memory consolidation, mediated by coordinated network activity during sharp-wave ripple (SWR) events. Despite the link between SWRs and hippocampal plasticity, little is known about how network state affects information processing in dendrites, the primary sites of synaptic input integration and plasticity. Here, we monitored somatic and basal dendritic activity in CA1 pyramidal cells in behaving mice using longitudinal two-photon calcium imaging integrated with simultaneous local field potential recordings. We found immobility was associated with an increase in dendritic activity concentrated during SWRs. Coincident dendritic and somatic activity during SWRs predicted increased coupling during subsequent exploration of a novel environment. In contrast, somatic-dendritic coupling and SWR recruitment varied with cells' tuning distance to reward location during a goal-learning task. Our results connect SWRs with the stabilization of information processing within CA1 neurons and suggest that these mechanisms may be dynamically biased by behavioral demands.
Asunto(s)
Hipocampo , Consolidación de la Memoria , Animales , Región CA1 Hipocampal/fisiología , Hipocampo/fisiología , Ratones , Neuronas , Células Piramidales/fisiologíaRESUMEN
Episodic memory requires linking events in time, a function dependent on the hippocampus. In "trace" fear conditioning, animals learn to associate a neutral cue with an aversive stimulus despite their separation in time by a delay period on the order of tens of seconds. But how this temporal association forms remains unclear. Here we use two-photon calcium imaging of neural population dynamics throughout the course of learning and show that, in contrast to previous theories, hippocampal CA1 does not generate persistent activity to bridge the delay. Instead, learning is concomitant with broad changes in the active neural population. Although neural responses were stochastic in time, cue identity could be read out from population activity over longer timescales after learning. These results question the ubiquity of seconds-long neural sequences during temporal association learning and suggest that trace fear conditioning relies on mechanisms that differ from persistent activity accounts of working memory.
Asunto(s)
Aprendizaje por Asociación/fisiología , Hipocampo/fisiología , Memoria Episódica , Red Nerviosa/fisiología , Animales , Conducta Animal , Región CA1 Hipocampal/fisiología , Condicionamiento Operante , Señales (Psicología) , Miedo/psicología , Hipocampo/citología , Procesamiento de Imagen Asistido por Computador , Memoria a Corto Plazo/fisiología , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiología , OptogenéticaRESUMEN
Hippocampal pyramidal cells encode memory engrams, which guide adaptive behavior. Selection of engram-forming cells is regulated by somatostatin-positive dendrite-targeting interneurons, which inhibit pyramidal cells that are not required for memory formation. Here, we found that γ-aminobutyric acid (GABA)-releasing neurons of the mouse nucleus incertus (NI) selectively inhibit somatostatin-positive interneurons in the hippocampus, both monosynaptically and indirectly through the inhibition of their subcortical excitatory inputs. We demonstrated that NI GABAergic neurons receive monosynaptic inputs from brain areas processing important environmental information, and their hippocampal projections are strongly activated by salient environmental inputs in vivo. Optogenetic manipulations of NI GABAergic neurons can shift hippocampal network state and bidirectionally modify the strength of contextual fear memory formation. Our results indicate that brainstem NI GABAergic cells are essential for controlling contextual memories.
Asunto(s)
Aprendizaje por Asociación/fisiología , Neuronas GABAérgicas/fisiología , Núcleos del Rafe/fisiología , Animales , Femenino , Interneuronas/química , Interneuronas/fisiología , Masculino , Pruebas de Memoria y Aprendizaje , Ratones , Ratones Endogámicos C57BL , Inhibición Neural/fisiología , Células Piramidales/química , Células Piramidales/fisiología , Somatostatina/análisis , Somatostatina/fisiología , Ritmo TetaRESUMEN
Recent studies have shown that hippocampal "time cells" code for sequential moments in temporally organized experiences. However, it is currently unknown whether these temporal firing patterns critically rely on upstream cortical input. Here we employ an optogenetic approach to explore the effect of large-scale inactivation of the medial entorhinal cortex on temporal, as well as spatial and object, coding by hippocampal CA1 neurons. Medial entorhinal inactivation produced a specific deficit in temporal coding in CA1 and resulted in significant impairment in memory across a temporal delay. In striking contrast, spatial and object coding remained intact. Further, we extended the scope of hippocampal phase precession to include object information relevant to memory and behavior. Overall, our work demonstrates that medial entorhinal activity plays an especially important role for CA1 in temporal coding and memory across time.