Synaptic circuits for information processing along the central auditory pathway

2014-09-10Sound 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. For perception of sound to occur, the basic attributes of sound (e.g. location, intensity, duration, et al.) need to be extracted and represented by neurons in the central auditory pathway. The synaptic circuit mechanisms underlying the extracting of these sound information attributes, however, remain poorly understood. During my PhD studies, I applied in vivo whole cell voltage clamp recording technique in studying how fusiform neurons in the Dorsal Cochlear Nucleus (DCN) of rat integrate excitatory and inhibitory synaptic inputs and generate novel spike patterns that presumably can encode intensity and temporal properties of sound information. In an independent but related project, I used head-fixed awake mice as a model to study how sound information processing could be modulated by different animal behavioral states. ❧ In my first project, we carried out in vivo whole-cell recordings from pyramidal neurons in the rat DCN, where intensity selectivity first emerges along the auditory pathway. Our results revealed that intensity-selective cells received fast-saturating excitation but slow-saturating inhibition with intensity increments, whereas in intensity-nonselective cells excitation and inhibition were similarly slow-saturating. The differential intensity tuning profiles of the non-intensity-tuned excitation and inhibition qualitatively determined the intensity selectivity of output responses. In addition, the selectivity was further strengthened by significantly lower excitation/inhibition ratios at high intensity levels compared to intensity-nonselective neurons. Our results demonstrate that intensity-selectivity in the DCN is generated by extracting the difference between tuning profiles of intensity-nonselective excitatory and inhibitory inputs, which we propose can be achieved through a differential circuit mediated by feedforward inhibition. ❧ In my second project, we studied how different temporal firing patterns (primary-like, pauser and buildup) were generated in pyramidal neurons in the rat DCN. We found that “primary-like” neurons received strong fast-rising excitation, whereas “pauser” or “buildup” neurons received accumulating excitation with a relatively weak fast rising phase followed by a slow rising phase. Pauser cells had stronger fast-rising excitation than buildup cells. On the other hand, inhibitory inputs to the three types of cells exhibited similar temporal patterns with a strong fast-rising phase. Dynamic-clamp recordings demonstrated that the differential temporal patterns of excitation could primarily account for the different discharge patterns. In addition, discharge patterns in a single neuron varied in a stimulus-dependent manner, which could be attributed to a modulation of excitation/inhibition ratio. Further studies of excitatory inputs to vertical and cartwheel cells suggested that fast-rising and accumulating excitation are separately conveyed by auditory nerve and parallel fibers respectively. The differential summation of excitatory input from two sources may thus contribute to the generation of response diversity. ❧ In my third project, we studied how transient offset response was generated in DCN fusiform cells. We found that in off responding neurons, their excitatory input started to decay later than inhibitory input did. This sharp increase of net excitation at sound offset caused the strong offset depolarization. Shortly after this offset depolarization, a second phase of inhibitory input accounted for the transient feature of the offset depolarization. Our results demonstrate that a fine temporal interaction of excitatory and inhibitory inputs can generate precisely timed off response in the rat DCN. ❧ In my fourth project, we developed in vivo whole cell voltage-clamp recording techniques in the auditory cortex of head-fixed awake mouse. We reported that sensory-evoked spike responses of layer 2/3 (L2/3) excitatory cells were scaled down with preserved sensory tuning when animals transitioned from quiescence to active behaviors, while L4 and thalamic responses were unchanged. Whole-cell voltage-clamp recordings further revealed that tone-evoked synaptic excitation and inhibition exhibited a robust functional balance. Changes of behavioral state caused scaling down of excitation and inhibition at an approximately equal level in L2/3 cells, but no synaptic changes in L4 cells. This laminar-specific gain control could be attributed to an enhancement of L1-mediated inhibitory tone, with L2/3 parvalbumin inhibitory neurons suppressed as well. Thus, L2/3 circuits can adjust the salience of output in accordance with momentary behavioral demands while maintaining the sensitivity and quality of sensory processing