From elementary synaptic circuits to information processing in primary auditory cortex

Abstract

A key for understanding how information is processed in the cortex is to unravel the dauntingly complex cortical neural circuitry. Recent technical innovations, in particular the in vivo whole-cell voltage-clamp recording techniques, make it possible to directly dissect the excitatory and inhibitory inputs underlying an individual cortical neuron's processing function. This method provides an essential complement to conventional approaches, with which the transfer functions of the neural system are derived by correlating neuronal spike outputs to sensory inputs. Here, we intend to introduce a potentially systematic strategy for resolving the structure of functional synaptic circuits. As complex circuits can be built upon elementary modules, the primary focus of this strategy is to identify elementary synaptic circuits and determine how these circuit units contribute to specific processing functions. This review will summarize recent studies on functional synaptic circuits in the primary auditory cortex, comment on existing experimental techniques for in vivo circuitry studies, and provide a perspective on immediate future directions.

Fig. 1. Schematic diagrams of cortical circuits

A. Upper: a general neural network. Blue and triangle, principal cell; red and circle, inhibitory cell. Thin line, axon; thick line, dendrite; dot, synapse. Lower: the connectivity of this network can be described by a matrix with synaptic strength of synapses between each pair of neurons as individual elements. B. Columnar and laminar processing in auditory cortex. Layer 4 (L4) and Layer 6 (L6) are recipient layers of thalamic inputs. Layer 2/3 (L2/3) and Layer 5 (L5) send outputs to other cortical regions and subcortical nuclei respectively. L6 sends corticothalamic feedback. C. A simplified input circuit for a L4 neuron.

Fig. 2

In vivo voltage-clamp recording to dissect different components of input. Excitatory and inhibitory components are separated by clamping the membrane potential of the recorded neuron at two different voltages. Thalamocortical inputs are further isolated by silencing the cortex. Cell morphology is recovered by post hoc histological staining.

Fig. 3. Diverse cortical functional circuits

A. A schematic diagram of a canonical circuit in Layer 4 of the primary auditory cortex (A1). Triangle, excitatory neuron; circle, inhibitory neuron. The frequency tuning of each connection is also presented along the projections. Gray curve depicts the frequency tuning curve. The thalamic and feedforward inhibitory inputs have a broad tuning, while the recurrent excitatory input has a sharp tuning. Together, the summed input exhibits a sharp frequency representation. B. A “silent” circuit in Layer 6 of A1. The recorded neuron is not directly innervated by thalamic neurons. Instead, it receives disynaptic excitatory input. C. A circuitry mechanism for cortical FM direction selectivity. The recorded neuron has a low CF and prefers upward FM sweeps. The spectral distribution of its excitatory inputs is skewed to low frequency side, and that of inhibition inputs is relatively broader and less skewed. D. A hypothesized circuit for intensity-tuned neurons in Layer 4 of non-monotonic zone (NM), which is adjacent to A1. The recorded neuron receives intensity-tuned thalamic input (green), and non-intensity-tuned inhibitory input from interneurons which are innervated by non-intensity-tuned thalamic neurons. The amplitude-intensity tuning curves for each type of input and the summed input are shown. Te and Ti represent the latencies of thalamic and inhibitory inputs. Their difference reduces as intensity increases (left), which further contributes to the sharpening of intensity selectivity of the recorded neuron.

Fig. 4

A cortical excitatory neuron receives inhibitory input from a diversity of interneurons, which have differential subcellular targeting preferences.