While the hippocampus has been implicated in supporting the association among time-separated events,the underlying cellular mechanisms have not been fully clarified.Here,we combined in vivo multi-channel recording and...While the hippocampus has been implicated in supporting the association among time-separated events,the underlying cellular mechanisms have not been fully clarified.Here,we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning(tEBC)task.We found that the hippocampal interneurons exhibited conditioned stimulus(CS)-evoked sustained activity,which predicted the performance of conditioned eyeblink responses(CRs)in the early acquisition of the tEBC.Consistent with this,greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC.Moreover,optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC.In contrast,suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs.Our findings highlight the role of hippocampal interneurons in the tEBC,and point to a potential cellular mechanism subserving associative learning.展开更多
Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal...Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording;this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.展开更多
The deep cerebellar nuclei(DCN)integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning.However,the functional relevance of distinct neuronal subp...The deep cerebellar nuclei(DCN)integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning.However,the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood.Here,we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial(Vm)thalamus(DCNVm neurons),and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning(tEBC),a classical associative sensorimotor learning task.Upon conditioning,the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses(CRs).Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs,respectively.Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination.Furthermore,optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex,a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC.Together,our data highlights DCNVm neurons’function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.展开更多
The Penrose inequality estimates the lower bound of the mass of a black hole in terms of the area of its horizon.This bound is relatively loose for extremal or near extremal black holes.We propose a new Penrose-like i...The Penrose inequality estimates the lower bound of the mass of a black hole in terms of the area of its horizon.This bound is relatively loose for extremal or near extremal black holes.We propose a new Penrose-like inequality for static black holes involving the mass,area of the black hole event horizon and temperature.Our inequality includes the Penrose inequality as its corollary,and it is saturated by both the Schwarzschild and Reissner-Nordstr?m black holes.In the spherically symmetric case,we prove this new inequality by assuming both the null and trace energy conditions.展开更多
基金the National Natural Science Foundation of China(32071014)the Open Project Program of Brain and Intelligence Research Key Laboratory of Chongqing Education Commission(BIR2019001)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(31921003).
文摘While the hippocampus has been implicated in supporting the association among time-separated events,the underlying cellular mechanisms have not been fully clarified.Here,we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning(tEBC)task.We found that the hippocampal interneurons exhibited conditioned stimulus(CS)-evoked sustained activity,which predicted the performance of conditioned eyeblink responses(CRs)in the early acquisition of the tEBC.Consistent with this,greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC.Moreover,optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC.In contrast,suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs.Our findings highlight the role of hippocampal interneurons in the tEBC,and point to a potential cellular mechanism subserving associative learning.
基金supported by grants from the National Natural Science Foundation of China(31970957 and 31471078)the Shanghai Science and Technology Commission(19ZR1416600)a 2021-JCJQ-JJ-1089 fund.
文摘Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording;this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
基金This work was supported by grants from the National Natural Science Foundation of China(81871039)the Natural Science Foundation of Chongqing Municipality(cstc2019jcyj-msxmX0424)+1 种基金the Frontier Interdisciplinary Project of the College of Basic Sciences(2020JCZX02)the Special Training Program for Undergraduates of Army Medical University(2020XBK09 and 2021XBK45).
文摘The deep cerebellar nuclei(DCN)integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning.However,the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood.Here,we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial(Vm)thalamus(DCNVm neurons),and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning(tEBC),a classical associative sensorimotor learning task.Upon conditioning,the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses(CRs).Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs,respectively.Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination.Furthermore,optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex,a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC.Together,our data highlights DCNVm neurons’function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.
基金supported by the National Natural Science Foundation of China(Grant Nos.12005155,11875200,and 11935009)。
文摘The Penrose inequality estimates the lower bound of the mass of a black hole in terms of the area of its horizon.This bound is relatively loose for extremal or near extremal black holes.We propose a new Penrose-like inequality for static black holes involving the mass,area of the black hole event horizon and temperature.Our inequality includes the Penrose inequality as its corollary,and it is saturated by both the Schwarzschild and Reissner-Nordstr?m black holes.In the spherically symmetric case,we prove this new inequality by assuming both the null and trace energy conditions.
