Fear Conditioning Mediates The Plasticity Of Auditory Response Properties Of The Inferior Colliculus Neurons In Mouse

Fear conditioning can induce changes of plasticity in inferior colliculus(IC)neurons in human and animal.Previous research focuses on the changes in receptive field and the shift in best frequency(BF)about auditory plasticity.Few reports provide other response properties,such as first spike latency and response duration.In vitro experiments in our laboratory found that primary auditory cortex neurons had a higher proportion of persistent activity(PA)in conditioned mouse.Whether this phenomenon also exists in in vivo needs to be further explored.In this research,the changes of auditory plasticity induced by conditioned training were investigated,and various parameters related to acoustic response characteristics were measured and compared with the experimental results in brain slice.The main results are as follows:(1)After conditioned training,the response properties of IC neurons in the conditioned group to conditioned sound were significantly changed in comparison with the control group,which were shown as follows,the minimum threshold(MT)significantly decreased(p<0.001),the response duration significantly prolonged(p<0.001)and the spikes significantly increased(p<0.001).The MT,response duration and spikes were correlated with the freezing index(all p<0.05).The results showed that IC neurons were more sensitive to conditioned sound after fear conditioned training.Further comparison of the response properties of IC neurons in the conditioned group to the conditioned sounds and characteristic frequency(CF)sounds showed that the MT to the conditioned sounds in the conditioned group was higher than that to the CF sounds(p<0.001),and there was no significant difference in the response duration and the spikes(both,p>0.05).Those above results showed that IC neurons in the conditioned group were more sensitive to the conditioned sounds than those in the control group,but did not exceed the response to the CF sounds.(2)After conditioned training,IC neurons in mouse significantly decreased in the MT,significantly extended in the response duration,and significantly increased in the spikes in response to pure tone in the range of 3 kHz of conditioned sound frequency(all p<0.05),and no significant changes were observed in MT,response duration,and spikes beyond this range.It was speculated that the pure tone in the range of 3 kHz of conditioned sound frequency could activate the projection of the cholinergic nuclei into the IC.(3)The IC neurons in the conditioned group and the control group showed two kinds of response patterns under the pure sound stimulation:transient and ongoing.In the conditioned group,there were 78.7%(59/75)transient IC neurons and 21.3%(16/75)ongoing IC neurons.In naive group,there were 90.4%(75/83)transient IC neurons and 9.6%(8/83)ongoing IC neurons.Response duration to CF sound of 9.3%(7/75)IC neurons in the conditioned group was longer than acoustic stimulation duration.Response duration to conditioned sound of 11.8%(4/34)IC neurons in the conditioned group was longer than acoustic stimulation duration,whereas the IC neurons in control mouse did not show this phenomenon.It was speculated that this phenomenon was related to the excitatory input generated by activation of cholinergic nuclei,but the response duration in in vivo was shorter than that of brain slices.After conditioned training,IC neurons in mouse were more sensitive to the pure tone in the range of 3 kHz of conditioned sound frequency,which may be due to topological structure inside the cholinergic nucleus.This is helpful for the selective attention of animals to the sound signal.After conditions training,the response duration of IC neurons can be slightly longer than acoustic stimulation duration,whereas there were high-frequency discharges lasting for tens of seconds in brain slices.We suggest that PA could be regarded as the representation of learning-induced auditory plasticity at the cellular level.Inactivation of transmitter and a balance between excitation and inhibitory input exist in the brain in in vivo,therefore the performance of PA at the global level is not obvious as in vitro.