The Characteristics Of Acoustic Response In Medial Prefrontal Cortex And Its Role In Auditory Fear Conditioning

Learning from severe stressors is considered a necessary condition for the survival of all types of animals.Therefore,in the past few decades,the mechanism of conditional fear has been extensively and deeply studied.Neutral pure tone as a conditional stimulus(CS)with unconditional stimulu(US)of the skin of the foot or leg is a classical conditional fear model,ie auditory fear conditioning model.The limbic system is sensitive to stress.The prefrontal cortex is an important part of the limbic system and is called the "headquarters" of the brain.The prelimbic cortex(PL)plays an important role in the formation and consolidation of fear memory.However,how prefrontal cortex work in processing acoustic information especially the non-specific and specific ones remains poorly studied.Clearly,before and after the establishment of auditory fear conditioning,little is known about the changes in the acoustic responses of prefrontal cortical neurons and their mechanisms.In the initial part of study,we investigated the response to acoustic stimulation in awaken mice’s prefrontal cortex using in vivo patch clamp recording.It was through large sample studies to single neuron that we found that(1)reacting to acoustic imformation in neurons of the anterior cingulate cortex(ACC),prelimbic cortex(PL),and infralimbic cortex(IL)show little difference.They were sensitive to the noise and all characterized by responsing to one or two relatively fixed acoustic frequency at high intensity of pure tone;(2)there exist two kinds of acoustic relative neuron in medial prefrontal cortex,type Ⅰ and type Ⅱ.It was showed that the action potential release rate of both kinds of neuron increased straightly followed by the sound intensity’increasing,reaching the maximum at the highest sound intensity,however,the latency of the acoustic response decreased as the sound intensity’increasing;(3)various types of neurons recorded,especially type Ⅰ and type Ⅱ neurons were mainly distributed in PL,followed by ACC,and IL were least.This may indicate that the distribution density of acoustically related neurons in PL is greater than that of the other two layers;(4)neurons with greater signal-to-noise ratio are more likely to respond to tone;(5)after PL injection of retrograde tracer,there was no obvious expression in the auditory cortex,but mainly concentrated in the gigantocellular reticular nucleus of the contralateral brain stem.This anatomical basis suggests that the afferent fibers of PL mainly come from non-specific projection systems,consistent with the predominant intensity response of prefrontal cortex neurons.Then we used c-Fos to observe that the number of positive neurons in PL neurons was significantly higher than that before training.The local field potential was then used to measure the changes of threshold and amplitude before and after training in the same position.It was found that the threshold decreased after training and the amplitude increased.Finally,we used a random sampling measurement method,first measured one side of the PL and then the other side of the PL after training,and each side only sampled the side 10 successful sealed neurons.We found that the proportion of type Ⅰ neurons in PL after training was significantly higher,and the signal to noise ratio of type Ⅰ neurons after training increased,while the threshold value decreased.Therefore,it is not difficult to draw the following conclusions:(1)fear training can indeed stimulate PL neurons,which may have a relationship with fear formation;(2)fear conditioning leads to a decrease in the threshold of neurons and an increase in signal-to-noise ratio;(3)the proportion of type Ⅰ neurons(associated with sound)increased significantly after fear conditioning training,which may cause increased sensitivity to sound.Previous studies and related pharmacological studies have shown that adrenergicβ receptors play an important role in the establishment and consolidation of memory after fear conditioning training.Therefore,in the single-cell recording of PL neurons,the adrenalin β agonist(isoproterenol hydrochloride)was administered locally.The results showed that the signal-to-noise ratio of response of PL neurons to noise stimulation increased,and the response threshold decreased,similar to the effect of fear conditioning training.In summary,in this experiment,the neurons in the medial prefrontal cortex of awake mice were recorded by in vivo patch-clamp recording and local field potential recording,combined with c-Fos staining,retrograde tracing,topical administration,and behavioral studies.The prefrontal information processing characteristics,auditory information input loop,and role in fear learning provide experimental and theoretical basis for studying how the prefrontal lobe participates in the processing of auditory information and the processing of related neural circuits,thereby expanding hearing Information edge system processing rules.In this experiment,the neurons in the medial prefrontal cortex of awake mice were recorded by in vivo patch-clamp recording and local field potential recording,combined with c-Fos staining,retrograde tracing,topical administration,and behavioral studies.We systematically studied the acoustic information processing characteristics of the prefrontal cortex and the changes after conditional fear training.This study provides experimental and theoretical basis for studying how the medial prefrontal cortex participates in the processing of auditory information and the processing of related neural circuits,thus expanding the cognition of the limbic system.