Survival depends on a balance between seeking rewards and avoiding potential threats, but the neural circuits that regulate this motivational conflict remain largely unknown. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited during conflict. Inactivation of aPVTCRF neurons during conflict biases animal’s response toward food, whereas activation of these cells recapitulates the food-seeking suppression observed during conflict. aPVTCRF neurons project densely to the nucleus accumbens (NAc), and activity in this pathway reduces food seeking and increases avoidance. In addition, we identified the ventromedial hypothalamus (VMH) as a critical input to aPVTCRF neurons, and demonstrated that VMH-aPVT neurons mediate defensive behaviors exclusively during conflict. Together, our findings describe a hypothalamic-thalamostriatal circuit that suppresses reward-seeking behavior under the competing demands of avoiding threats.

Both clinical and experimental studies have reported that mild traumatic brain injury (mTBI) can result in cognitive impairments in the absence of overt brain damage. Whether these impairments result from neuronal dysfunction/altered plasticity is an area that has received limited attention. In this study, we recorded activity of neurons in the cornu Ammonis (CA)1 subfield of the hippocampus in sham and mild lateral fluid percussion injured (mFPI) rats while these animals were performing an object location task. Electrophysiology results showed that the number of excitatory neurons encoding spatial information (i.e., place cells) was reduced in mFPI rats, and that these cells had broader and less stable place fields. Additionally, the in-field firing rate of place cells in sham operated, but not in mFPI, animals increased when objects within the testing arena were moved. Immunostaining indicated no visible damage or overall neuronal loss in mFPI brain sections. However, a reduction in the number of parvalbumin-positive inhibitory neurons in the CA1 subfield of mFPI animals was observed, suggesting that this reduction could have influenced place cell physiology. Alterations in spatial information content, place cell stability, and activity in mFPI rats coincided with poor performance in the object location task. These results indicate that altered place cell physiology may underlie the hippocampus-dependent cognitive impairments that result from mTBI.

Sleep is regulated by environmental factors including temperature, but the neural circuits that receive the sensory signal and mediate the regulation remain unclear. We examined how cold could influence Drosophila sleep patterns and its neural mechanism. The results showed that Drosophila has more sleep duration, less sleep latency and deeper sleep depth under cold condition. We identified the Insulin-producing Cells (IPCs) can be activated by cold, and receive the cold signal from the 11216 cold-sensing neuron without a direct synaptic connection. Elevation of IPCs' sensitivity to cold impairs the sleeppromoting effect of cold while blocking of IPCs enhance the effect mostly on sleep circadian, suggesting that the cold activated IPCs have a compensative role in sleep regulation. Our finding revealed a potential neural circuit that help maintain sleep circadian in detrimental environment and may give new insight to the complicated sleep regulation mechanism.

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Associative learning requires the activation of protein kinases with distinct temporal dynamics. Learning protocols with computationally designed intertrial intervals (ITIs) that maximize the interaction between fast-activated protein kinase A (PKA) and slow-activated extracellular signal-regulated kinase (ERK) enhance nonassociative learning in Aplysia. Here, we tested whether an optimal learning protocol with irregular ITIs, predicted computationally to increase the overlap between PKA and ERK signaling in rat hippocampus, would enhance associative learning in mammals. We simulated ~1000 training protocols with irregular ITIs and identified an optimal protocol, predicted to induce stronger associative learning than standard protocols with fixed ITIs. With auditory fear conditioning, we showed that male adult rats exposed to the optimal conditioning protocol exhibited stronger fear memory retrieval and impaired fear memory extinction, compared to rats that received either massed or spaced conditioning protocols with fixed ITIs. With fear extinction, we likewise observed that fear conditioned rats exposed to the optimal extinction protocol showed improved extinction of contextual fear memory, compared to rats that received standard extinction protocols. Together, these findings demonstrate the capacity of a behavioral intervention driven by a computational model of memory-related signaling pathways to enhance associative learning in mammals and may provide greater insight into strategies to improve cognition in humans.

No abstract