Seizures are caused by increased neuronal firing activity resulting from reduced inhibitory effect and enhancement of inhibitory modulation to suppress this activity is used as a therapeutic tool.However,recent experi...Seizures are caused by increased neuronal firing activity resulting from reduced inhibitory effect and enhancement of inhibitory modulation to suppress this activity is used as a therapeutic tool.However,recent experiments have shown a counterintuitive phenomenon that inhibitory modulation does not suppress but elicit post-inhibitory rebound(PIR)spike along with seizure to challenge the therapeutic tool.The nonlinear mechanism to avoid the PIR spike can present theoretical guidance to seizure treatment.This paper focuses on identifying credible bifurcations that underlie PIR spike by modulating multiple parameters in multiple theoretical models.The study identifies a codimension-2 bifurcation called saddle-node homoclinic orbit(SNHOB),which is an intersection between saddle node bifurcation on invariant cycle(SNIC)and other two bifurcations.PIR spike cannot be evoked for the SNIC far from the SNHOBbut induced for the SNIC close to the SNHOB,which extends the bifurcation condition for PIR spike from the well-known Hopf to SNIC.Especially,in a thalamic neuron model,increases of conductance of T-type Ca^(2+)(TC a)channel induce SNIC bifurcation approaching to the SNHOB to elicit PIR spikes,closely matching experimental results of the absence seizure or Parkinson diseases.Such results imply that,when inhibition is employed to relieve absence seizure and Parkinson diseases related to PIR spike,modulating SNIC to get far from the SNHOBto avoid PIR spike is the principle.The study also addresses the complex roles of TCacurrent and comprehensive relationships between PIR spike and nonlinear conceptions such as bifurcation types and shapes of threshold curve.展开更多
Post-inhibitory rebound(PIR)spike,which has been widely observed in diverse nervous systems with different physiological functions and simulated in theoretical models with class-2 excitability,presents a counterintuit...Post-inhibitory rebound(PIR)spike,which has been widely observed in diverse nervous systems with different physiological functions and simulated in theoretical models with class-2 excitability,presents a counterintuitive nonlinear phenomenon in that the inhibitory effect can facilitate neural firing behavior.In this study,a PIR spike induced by inhibitory stimulation from the resting state corresponding to class-3 excitability that is not related to bifurcation is simulated in the Morris–Lecar neuron.Additionally,the inhibitory self-feedback mediated by an autapse with time delay can evoke tonic/repetitive spiking from phasic/transient spiking.The dynamical mechanism for the PIR spike and the tonic/repetitive spiking is acquired with the phase plane analysis and the shape of the quasi-separatrix curve.The result extends the counterintuitive phenomenon induced by inhibition to class-3 excitability,which presents a potential function of inhibitory autapse and class-3 neuron in many neuronal systems such as the auditory system.展开更多
Despite extensive characterization of sex differences in the medial preoptic area(mPOA)of the hypothalamus,we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically,es...Despite extensive characterization of sex differences in the medial preoptic area(mPOA)of the hypothalamus,we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically,especially in terms of neuronal firing and behavioral pattern generation.In this study,by performing whole-cell patch clamp recordings of the mPOA,we investigated the influences of sex,cell type,and gonadal hormones on the electrophysiological properties of mPOA neurons.Notably,we uncovered significant sex differences in input resistance(male>female)and in the percentage of neurons that displayed post-inhibitory rebound(male>female).Furthermore,we found that the current mediated by the T-type Ca^(2+)channel(IT),which is known to underlie post-inhibitory rebound,was indeed larger in male mPOA neurons.Thus,we have identified salient electrophysiological properties of mPOA neurons,namely IT and post-inhibitory rebound,that are male-biased and likely contribute to the sexually dimorphic display of behaviors.展开更多
基金the National Natural Science Foundation of China(Grant Nos.12072236,11872276,and11802086)the Postdoctoral Research Project of Henan Province,China(Grant No.19030095)the Science and Technology Development Program of Henan Province,China(Grant No.212102210543)。
文摘Seizures are caused by increased neuronal firing activity resulting from reduced inhibitory effect and enhancement of inhibitory modulation to suppress this activity is used as a therapeutic tool.However,recent experiments have shown a counterintuitive phenomenon that inhibitory modulation does not suppress but elicit post-inhibitory rebound(PIR)spike along with seizure to challenge the therapeutic tool.The nonlinear mechanism to avoid the PIR spike can present theoretical guidance to seizure treatment.This paper focuses on identifying credible bifurcations that underlie PIR spike by modulating multiple parameters in multiple theoretical models.The study identifies a codimension-2 bifurcation called saddle-node homoclinic orbit(SNHOB),which is an intersection between saddle node bifurcation on invariant cycle(SNIC)and other two bifurcations.PIR spike cannot be evoked for the SNIC far from the SNHOBbut induced for the SNIC close to the SNHOB,which extends the bifurcation condition for PIR spike from the well-known Hopf to SNIC.Especially,in a thalamic neuron model,increases of conductance of T-type Ca^(2+)(TC a)channel induce SNIC bifurcation approaching to the SNHOB to elicit PIR spikes,closely matching experimental results of the absence seizure or Parkinson diseases.Such results imply that,when inhibition is employed to relieve absence seizure and Parkinson diseases related to PIR spike,modulating SNIC to get far from the SNHOBto avoid PIR spike is the principle.The study also addresses the complex roles of TCacurrent and comprehensive relationships between PIR spike and nonlinear conceptions such as bifurcation types and shapes of threshold curve.
基金the National Natural Science Foundation of China(Grant Nos.11802085,11872276,and 12072236)the Science and Technology Project of Guangzhou(Grant No.202102021167)+1 种基金GDAS’Project of Science and Technology Development(Grant No.2021GDASYL20210103088)the Science and Technology Development Program of Henan Province,China(Grant No.212102310827)。
文摘Post-inhibitory rebound(PIR)spike,which has been widely observed in diverse nervous systems with different physiological functions and simulated in theoretical models with class-2 excitability,presents a counterintuitive nonlinear phenomenon in that the inhibitory effect can facilitate neural firing behavior.In this study,a PIR spike induced by inhibitory stimulation from the resting state corresponding to class-3 excitability that is not related to bifurcation is simulated in the Morris–Lecar neuron.Additionally,the inhibitory self-feedback mediated by an autapse with time delay can evoke tonic/repetitive spiking from phasic/transient spiking.The dynamical mechanism for the PIR spike and the tonic/repetitive spiking is acquired with the phase plane analysis and the shape of the quasi-separatrix curve.The result extends the counterintuitive phenomenon induced by inhibition to class-3 excitability,which presents a potential function of inhibitory autapse and class-3 neuron in many neuronal systems such as the auditory system.
基金This work was supported by Grants from the National Natural Science Foundation of China(31871066,31922028 and 31900721)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32000000).
文摘Despite extensive characterization of sex differences in the medial preoptic area(mPOA)of the hypothalamus,we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically,especially in terms of neuronal firing and behavioral pattern generation.In this study,by performing whole-cell patch clamp recordings of the mPOA,we investigated the influences of sex,cell type,and gonadal hormones on the electrophysiological properties of mPOA neurons.Notably,we uncovered significant sex differences in input resistance(male>female)and in the percentage of neurons that displayed post-inhibitory rebound(male>female).Furthermore,we found that the current mediated by the T-type Ca^(2+)channel(IT),which is known to underlie post-inhibitory rebound,was indeed larger in male mPOA neurons.Thus,we have identified salient electrophysiological properties of mPOA neurons,namely IT and post-inhibitory rebound,that are male-biased and likely contribute to the sexually dimorphic display of behaviors.
