Synaptic Mechanism Of Auditory Information Processing In Awake Mouse Primary Auditory Cortex

Auditory information is transmitted into electrical signals in the inner ear and these signals,i.e.action potentials,are passed and processed along the central auditory pathway.Auditory cortex,an important member of auditory pathway,plays an important role in auditory information processing.In auditory cortex,there are millions of neurons.The response properties and underlying synaptic mechanisms of these properties of neurons to different sound stimuli are still unclear.During my PhD study,I used primary auditory cortex(Al)of awake mice as a model and applied in vivo cell attached recording and whole cell recording to study the response properties and synaptic mechanisms of these properties of AI neurons to different sound stimuli and how sound information processing could be modulated by behavioral state.In my first project,to decipher brain functions requires understanding of general principles for how the external world is represented by neuronal populations in sensory cortex.In awake mouse primary auditory cortex,we surprisingly discovered that predominant neurons in Iayer2/3 were dormant,showing no spike responses to sound stimuli of any fundamental category,while the remaining neurons responded to a broad variety of sound eategories.In contrast,few parvalbumin inhibitory neurons were dormant.Dormant neurons all received sound-evoked synaptic inputs,but failed to spike due to a weak excitatory drive and low exeitation/inhibition(E/I)ratio.The cortical sparseness developmentally emerged in an acoustic-experience dependent manner,along with differentiation of E/I ratio from a unimodal to binodal distribution.Furthermore,the sparseness can be down-regulated by associative learning in a stimulus-specific manner,through modulating layer-1 inhibitory circuits.Thus,recruitments of on-reserve neurons for sensory representation provide an efficient mechanism for functional evolution and plasticity of the brain.In my second project,we already know that Band-passed noise(BPN)stimuli are prevalent in communication sounds.Tuning of auditory neurons for bandwidth of BPN may be functionally important for the perception of these sounds.In awake mouse primary auditory cortex(Al),we found that excitatory neurons exhibit decreasing,increasing or flat bandwidth tuning,and there is an enhancement of tuning strength from layer 4 to layer 2/3.On the other hand,most parvalbumin(PV)positive inhibitory neurons had flat tuning.Sequential cell-attached and whole-cell voltage clamp recordings from the same cell revealed that the tuning properties of excitatory neurons were inherited from excitation they received,whereas in all neurons inhibition had flat tuning.Importantly,the tuning strength of spike response was enhanced compared with excitation.Our neuron modeling work demonstrate an important role of flat(untuned)inhibition in enhancing bandwidth tuning of spike responses.Our study,for the first time,elucidated synaptic mechanisms underlying bandwidth tuning of auditory cortical neurons.