Parvalbumin-positive(PV^(+))interneuron dysfunction is believed to be linked to autism spectrum disorder(ASD),a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors.However,the mech...Parvalbumin-positive(PV^(+))interneuron dysfunction is believed to be linked to autism spectrum disorder(ASD),a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors.However,the mechanisms behind PV^(+)interneuron dysfunction remain largely unclear.Here,we found that a deficiency of Biorientation Defective 1(Bod1)in PV^(+)interneurons led to an ASD-like phenotype in Pvalb-Cre;Bod1f/f mice.Mechanistically,we observed that Bod1 deficiency induced hypoactivity of PV^(+)interneurons and hyperactivity of calcium/calmodulin-dependent protein kinaseⅡalpha(CaMKⅡα)neurons in the medial prefrontal cortex,as determined by whole-cell patch-clamp recording.Additionally,Bod1 deficiency decreased the power of highgamma oscillation,assessed by in vivo multi-channel electrophysiological recording.Furthermore,we found that Bod1 deficiency enhanced the inwardly rectifying K^(+)current,leading to an increase in the resting membrane potential of PV^(+)interneurons.Importantly,the gain-of-function of Bod1 improved social deficits and stereotypical behaviors in Pvalb-Cre;Bod1f/f mice.These findings provide mechanistic insights into the PV^(+)interneuron dysfunction and suggest new strategies for developing PV^(+)interneuron-targeted therapies for ASD.展开更多
The olfactory bulb(OB) is the first relay station in the olfactory system.In the OB,mitral/tufted cells(M/Ts),which are the main output neurons,play important roles in the processing and representation of odor informa...The olfactory bulb(OB) is the first relay station in the olfactory system.In the OB,mitral/tufted cells(M/Ts),which are the main output neurons,play important roles in the processing and representation of odor information.Recent studies focusing on the function of M/Ts at the single-cell level in awake behaving mice have demonstrated that odor-evoked firing of single M/Ts displays transient/long-term plasticity during learning.Here,we tested whether the neural activity of M/Ts and sniffing patterns are dependent on anticipation and reward in awake behaving mice.We used an odor discrimination task combined with in vivo electrophysiological recordings in awake,head-fixed mice,and found that,while learning induced plasticity of spikes and beta oscillations during odor sampling,we also found plasticity of spikes,beta oscillation,sniffing pattern,and coherence between sniffing and theta oscillations during the periods of anticipation and/or reward.These results indicate that the activity of M/Ts plays important roles not only in odor representation but also in salience-related events such as anticipation and reward.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2022YFE0108600 to Y.M.L.)the National Natural Science Foundations of China(Grant Nos.82473918 and 82104162 to X.X.L.).
文摘Parvalbumin-positive(PV^(+))interneuron dysfunction is believed to be linked to autism spectrum disorder(ASD),a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors.However,the mechanisms behind PV^(+)interneuron dysfunction remain largely unclear.Here,we found that a deficiency of Biorientation Defective 1(Bod1)in PV^(+)interneurons led to an ASD-like phenotype in Pvalb-Cre;Bod1f/f mice.Mechanistically,we observed that Bod1 deficiency induced hypoactivity of PV^(+)interneurons and hyperactivity of calcium/calmodulin-dependent protein kinaseⅡalpha(CaMKⅡα)neurons in the medial prefrontal cortex,as determined by whole-cell patch-clamp recording.Additionally,Bod1 deficiency decreased the power of highgamma oscillation,assessed by in vivo multi-channel electrophysiological recording.Furthermore,we found that Bod1 deficiency enhanced the inwardly rectifying K^(+)current,leading to an increase in the resting membrane potential of PV^(+)interneurons.Importantly,the gain-of-function of Bod1 improved social deficits and stereotypical behaviors in Pvalb-Cre;Bod1f/f mice.These findings provide mechanistic insights into the PV^(+)interneuron dysfunction and suggest new strategies for developing PV^(+)interneuron-targeted therapies for ASD.
基金supported by the National Natural Science Foundation of China (31571082,31872771 and 31700895)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(16KJA180007)the Natural Science Foundation of Jiangsu Province (BK20170260)。
文摘The olfactory bulb(OB) is the first relay station in the olfactory system.In the OB,mitral/tufted cells(M/Ts),which are the main output neurons,play important roles in the processing and representation of odor information.Recent studies focusing on the function of M/Ts at the single-cell level in awake behaving mice have demonstrated that odor-evoked firing of single M/Ts displays transient/long-term plasticity during learning.Here,we tested whether the neural activity of M/Ts and sniffing patterns are dependent on anticipation and reward in awake behaving mice.We used an odor discrimination task combined with in vivo electrophysiological recordings in awake,head-fixed mice,and found that,while learning induced plasticity of spikes and beta oscillations during odor sampling,we also found plasticity of spikes,beta oscillation,sniffing pattern,and coherence between sniffing and theta oscillations during the periods of anticipation and/or reward.These results indicate that the activity of M/Ts plays important roles not only in odor representation but also in salience-related events such as anticipation and reward.
