Firing Activities Of PV Interneurons Modulate Local Field Potential Rhythms

Prefrontal cortex and hippocampus play an important role in cognitive function.Neurons that constitute these structures can be classified into two main groups,that is,excitatory pyramidal neurons and inhibitory interneurons.Pyramidal neurons constitute about 85% of the total neurons,and are implicated in the encoding of event information inputs.In contrast,interneurons constitute only about 15%,and are known to function in the process of learning and memory and other cognitive activities of the brain by participating in coordination of local neural network activities.Parvalbumin(PV)immunopositive interneurons are one of the most important subtypes of interneurons.At present,studies on PV interneurons have accumulated much works in the area of morphology,molecular biology,in vitro electrophysiology on brain slices,in vivo electrophysiology on anaesthetized animals and ethology.Whereas it has not been systematically observed and studied in the area of in vivo electrophysiology on conscious animals.We combine in vivo multi-channel recording technique with optoginetics technique to conduct synchronized recording across medial prefrontal cortex(m PFC)and dorsal hippocampal CA1(d CA1).We mainly focus on firing patterns of PV interneurons within these two areas,as well as the physiological functions and significances of their activities,in order to have knowledge of the function and mechanism of PV interneurons within different brain areas so as to enhance the recognition of information processing of cerebral local neural networks.In this study,PV–CRE mouse line was bred with Ai32 mouse line to create PV–Ch R2–EYFP mouse line in order to express channelrhodopsin-2(Chr2)specifically in PV interneurons.We recorded 250 and 132 neurons separately in the m PFC and d CA1 region of36 free moving PV–Ch R2–EYFP transgenetic mice.According to whether the neurons show action potential sequential responses to laser pulse stimuli,we identified 18 of the recorded m PFC suspected interneurons and 13 of the recorded d CA1 suspected interneurons to be PV interneurons,within which 4 m PFC–m PFC PV interneuron pairs,2 d CA1–d CA1 PV interneuron pairs and 7 m PFC–d CA1 PV interneuron pairs were recorded simultaneously.Analysis revealed that during animals' active wakefulness state,18 recorded m PFC PV interneurons are significantly phase locked to local field potential high frequency oscillation(HFO,here refer to oscillations higher than 100 Hz).a few(3/18)are phase locked to gamma oscillations(30–80 Hz).But none are phase locked to cortical theta oscillations(4–8 Hz).In the hippocampus,13 recorded PV interneurons are all phase locked to both hippocampal HFO and theta(4–12 Hz).In addition,nearly half(6/13)are phase locked to gamma.During the slow-wave sleep state,m PFC PV interneurons show well phase locked to delta,while d CA1 PV interneurons are phase locked to ripple but not delta.These features of in vivo firing patterns about relevance to rhythms of local field potential indicate that although both being PV interneurons,cortical and hippocampal PV interneurons have different in vivo firing patterns,and they should have different physiological function respectively.Cluster analysis of these recorded PV interneurons was taken based on features of firing pattens.It is revealed that m PFC PV interneurons are clustered into 2 groups,that is HFO related in higher and lower level.d CA1 PV interneurons are clustered into 3 groups,that is HFO/ripple related in higher/lower level and OFF(with a decrease in firing rate).These results above indicate that PV interneurons within the same region can belong to different function groups,whose diversity mainly embodied in relevance to local field potential high frequency rhythms(HFO/ripple).Further analysis on m PFC and d CA1 neural activity synchronism revealed that during active wakefulness state,HFOs in both areas showed a certain degree of synchronism.Meanwhile,it is revealed that frequency of PV interneuron synchronism firing events are significantly correlated to HFO power,and that synchronism of PV interneuron activities significantly increased during HFO events whose power is much higher.Besides,synchronism of PV interneuron activities is observed to increase during hippocampal ripple events under slow-wave sleep state.These findings suggest that simultaneously firing of m PFC and d CA1 PV interneuron may implicate in the modulation of HFO synchronism between both areas,and that synchronism of cortico-hippocampal PV interneuron activities during ripple events may implicate in the process of memory consolidation.In summary,PV interneurons between different brain areas have different in vivo firing patterns.Even those within the same area can have subtypes of firing patterns.m PFC PV interneurons are mainly involved in the regulation of local field potential HFO rhythm under awakeness.Being related to the above function,d CA1 PV interneurons are closely associated with local field potential ripple rhythm under unconsciousness as well.These results provide a basis for further understanding the regulation mechanism of local neural network activities.