Cellular Mechanism Underlying The Modulation Of Ventral Tegmental Area To Rat Primary Auditory Cortex

Objective：The primary auditory cortex (A1) receives and processes information inputs fromauditory thalamus. In auditory system, A1plays an important role in sound discrimination,sound processing and memory. The various forms of responses to sound stimulation of A1indicate that different modes of stimulation can evoke diverse neural electrophysiologicalactivities in brain and lead to distinct behavioral patterns.The brain reward system is absolutely essential for individuals to adapt the complexenvironment and survive. The mesolimbic dopaminergic system is the center of brainreward system. The ventral tegmental area (VTA) and nucleus accumbens (NAc) arestructural basis of mesolimbic dopaminergic system, and dopamine is the most importantneurotransmitter. There exist widespread projections between mesencephalic dopaminergicreward system and sensory cortex, and the representation of sensory information in thecortex is modulated by mesencephalic reward system. Moreover, the activation of VTA canrapidly change the tonotopic representation in primary auditory cortex.Previous electrophysiological studies proved that activation of reward system candramatically influence the neuronal activity in sensory cortex. It has been reported thatdopaminergic reward signals can selectively modulate the plasticity of visual and auditorycortices. Bao et al. found that after pairing a particular tone with electrical microstimulationof the VTA, the A1showed increased or decreased selectivity and enlarged or reducedcortical area representing the very sound stimulation, depending on the sequence of pairedsound and VTA stimulation. This indicate that VTA activation can change the biologicalsignificance of paired sensory stimulus. However, the understanding of how mesencephalicreward system modulate the neural activity and plasticity of A1is still limited. This maydue to the diverse biological functions of reward system, complex connections between mesencephalon and sensory cortex, various states and characteristics of responses in A1neurons. Moreover, previous studies using extracellular recording or pharmacologicalmethods only showed us the modulation effects of VTA on neuronal activities of A1, butcannot provide us the details of underlying mechanism of the interaction between VTA andA1. Clarify this mechanism will shed light on the relationship between the reward systemand sensory cortex, thus promote our understanding of the biological nature underlyinginformation processing in sensory cortex.Methods：Part I:We used multiple in vivo recording techniques to observe the characteristic of neuronalactivities of A1including local field potential (LFP), extracellular multi-unit activity(MUA), single-unit activity (SUA) and intracellular membrane potential. We furtherdescribed the distinct forms of responses that evoked by puretone/noise stimulation and thelate sound evoked responses in rat A1.Part II:We adopted in vivo extracellular recording technique to get the functional location ofA1. Then in vivo intracellular recording was used to study the influence of VTA activationon the excitatory and inhibitory post-synaptic potentials (EPSP and IPSP) of A1neurons.Results：Part I:1. The response thresholds of neurons with lower range of CF are relatively high, andneurons with higher range of CF usually have lower response thresholds.2. Distinct forms of responses could be evoked by puretone and noise stimulation inrat A1, and about10%A1neurons showed suppressive responses to noise and excitatoryresponses to puretone. The puretone evoked EPSP had longer duration and higher amplitudethan that of noise evoked EPSP.3. Around30%A1neurons performed both onset responses with short latencies andlate responses with long latencies. The results recorded by LFP, SUA and intracellularmembrane potential showed the latencies of late responses were far longer than the onsetones. Part II:1. The activation of VTA compressed the excitatory response window and shortenedthe duration of EPSP of A1neurons, but it promoted the neuronal firing precision andstrength.2. VTA activation shortened the duration of sound evoked EPSP of A1neurons, whilethe thalamic inputs and the excitability of A1neurons were not affected.3. VTA activation potentiated the level of hyperpolarization of post synaptic potentialsof A1neurons.Conclusion：It is a general characteristic that A1neurons exhibit late responses with long latencies.In vivo study showed that around30%A1neurons performed both onset responses withshort latencies and late responses with long latencies.The activation of VTA improved theneural activities of inhibitory microcircuits in A1, increased the inhibitory inputs topyramidal neurons, led to the enhanced and early arrived hyperpolarization, and promotedthe neuronal firing precision and strength in A1.