Parvalbumin Interneuron In Thalamic Reticular Nucleus Modulates Prepulse Inhibition And Latent Inhibition In Mice

Thalamic reticular nucleus(TRN)is a shell-like structure,which was mainly composed of GABAergic neurons.TRN lies between cortex and thalamus,and received inputs from both cortex and thalamus,but sent outputs only to thalamus.TRN was thought to play an important role in thalamocortical networks,which may have influences on many brain functions,such as sleep-wakefulness regulation,sensory gating,selection of sensory information and attention.And dysfunction of TRN may play a role in many kinds of mental disorder:schizophrenia,autism,attention deficit hyperactivity disorder,manic-depressive disorder.Schizophrenia is a severe mental illness,which brings a heavy burden to our society.The major symptoms of this disorder include sensory disturbance,perceptual disturbance and cognitive impairment.And the typical behavioral paradigms used in the studies of schizophrenia are sensory gating and latent inhibition(LI).Sensory gating is a fundamental brain function which may filter out redundant or unnecessary information in the brain,and make sure other brain functions functioning,such as prepulse inhibition.Impaired sensory gating is the main symptom of schizophrenia,it may cause overload of information flow in the brain,which in turns can induce some serious cognitive impairment.Latent inhibition(LI)is one of these cognitive functions.LI is the ability to acquire the pre-exposed stimulation as an irrelevant information during a conditional learning task.Impaired PPI and LI are the most common behavioral phenotypes in schizophrenia.Previous studies have found that TRN was closely related to schizophrenia.In one study about brain samples of clinical schizophrenia patients,they found decreased number and damaged structure of PV neurons in TRN.Other studies found that inhibition of TRN neurons can reduce sleep spindles density in animal,and decreased sleep spindles were common phenomena in the sleep architecture of schizophrenia patients.As for the relationship between TRN and sensory gating or LI,the evidence is not sufficient and the specific mechanism is not clear.In our study,we first demonstrate that PV interneuron in TRN plays an important role in the sensory gating-related behavior PPI,by the expression of the immediate early genes c-fos,and calcium activity recorded from awake pv-cre mice.After that,we used chemical genetic methods to inhibit the activity of PV interneuron in TRN,we found that the function of sensory gating was impaired,such as impaired PPI,and LI was also damaged.In chronic repetitive sleep deprivation model,the excitatory synaptic transmission of PV interneuron in TRN in mice was decreased,and PPI and LI were also damaged.Finally,by using electrophysiological techniques of isolated brain slices,we found PV interneuron in TRN fires action potential in burst ways when they received inputs from medial geniculate body(MGB),a main section of auditory transmission in thalamus.Then we injected NiCl2,a T-type calcium channel blocker,into the TRN of mice by stereotaxic technique to inhibit the burst discharges in TRN.We found that blocking the burst discharges could significantly inhibit PPI and LI.These results can further promote the study of the physiological function of thalamic reticular nucleus and provide a theoretical basis for the development of new drug targets for psychiatric treatment.