Optogenetics publications

How neuronal firing within a circuit encodes behavioural intensity, like running speed, is largely unknown. Projections from temporal association cortex (TeA) and superior colliculus (SC) to dorsal periaqueductal grey (dPAG) circuit can both trigger running behaviour. Using in vivo loose-patch recordings with circuit manipulations in mice, we quantified a firing - speed relationship and established its encoding model. Here, we report two behavioural patterns induced by circuit activation: backing away and rebound running. Mechanistically, dPAG CaMKIIα neurons receiving inputs from either TeA or SC, function as distinct “behavioural units”, controlling two “unit behaviours” of running and backing away, respectively. The unidirectional inhibition from the backing away unit to the running unit is mediated by somatostatin (SOM) neurons in dPAG, enabling transitions among four behavioural states: running, backing away, stopping, and rebound running. Both running and backing away behaviours follow a unified motor encoding model, quantified by a single-phase association equation.

A central goal in neuroscience is to clarify how neural circuits translate sensory input into adaptive behaviours. Although unisensory evoked escape circuits in mice are well defined, it remains unclear whether a single nucleus contains specialized sensory, sensory‒motor decision, and motor command neurons for escapes driven by distinct sensory cues, and how these neurons form functional microcircuits. Using multiple sensory stimuli in mice, we identified the temporal association cortex (TeA) as a critical escape hub. Combining in vivo electrophysiology, optogenetics and chemogenetics, we characterized three distinct neuron subtypes within TeA layer 5 (L5) CaMKII neurons that correspond to these three functional classes. Intratelencephalic (IT) neurons serve as sensory‒motor decision neurons, while layer matched pyramidal tract (PT) neurons projecting to the dorsal periaqueductal grey (dPAG) act as motor command neurons. We reveal a laminar IT–PT microcircuit that converts sensory input into sensory-motor decisions and commands for escape locomotion.

Fear retrieval is fundamental for animals to rapidly enter a self-defense state, which enhances their survival rate. Although the cellular mechanisms and neural circuits underlying fear retrieval have been relatively well studied, particularly in classic fear-related nuclei such as the amygdala, the neural circuits and intrinsic microcircuits of some non-classical fear-related nuclei remain poorly understood. A disinhibitory microcircuit in the temporal association cortex (TeA) was identified in this study, demonstrating a critical role in fear retrieval. Additionally, the response of the TeA to fear retrieval is largely driven by acetylcholine (Ach), which then relay information to the tail of striatum (TS) to mediate freezing behavior. Together, these findings demonstrate the essential role of the TeA and its microcircuit in auditory fear retrieval in response to pure tones, providing new insights into the mechanisms of fear retrieval in the cortex.