Imbalance of excitation and inhibition at threshold level in the auditory cortex

Abstract

The interplay of cortical excitation and inhibition is a fundamental feature of cortical information processing. Excitation and inhibition in single cortical neurons are balanced in their response to optimal sensory stimulation due to thalamocortical feedforward microcircuitry. It is unclear whether the balance between cortical excitation and inhibition is maintained at the threshold stimulus level. Using in vivo whole-cell patch-clamp recording of thalamocortical recipient neurons in the primary auditory cortex of mice, we examined the tone-evoked excitatory and inhibitory postsynaptic currents at threshold levels. Similar to previous reports, tone induced excitatory postsynaptic currents when the membrane potentials were held at 70 mV and inhibitory postsynaptic currents when the membrane potentials were held at 0 mV on single cortical neurons. This coupled excitation and inhibition is not demonstrated when threshold-level tone stimuli are presented. In most cases, tone induced only excitatory postsynaptic current. The best frequencies of excitatory and inhibitory responses were often different and thresholds of inhibitory responses were mostly higher than those of excitatory responses. Our data suggest that the excitatory and inhibitory inputs to single cortical neurons are imbalanced at the threshold level. This imbalance may result from the inherent dynamics of thalamocortical feedforward microcircuitry.

Keywords: auditory cortex; excitatory-inhibitory imbalance; in vivo whole cell patch; minimal threshold; thalamocortical model.

Figure 1

Tone-evoked postsynaptic currents (Inset) are plotted as the function of holding membrane potentials in one neuron (repeated 5 times). Since the IPSC commonly has a 1–4 ms delay from the EPSC (Wehr and Zador, 2003), two time windows of 0–1 ms (Gray symbols) and 5–7 ms (Black symbols) from the response onset were selected for EPSC and IPSC measurements. The postsynaptic currents were linearly correlated to the holding potentials (R² = 0.98 and R² = 0.99, respectively).

Figure 2

Examples of EPSCs and IPSCs of 2 AI neurons in response to tones around BF/MT. The BF/MT of EPSC and IPSC were identical in Neuron A (left) but not in Neuron B (right) as indicated by the dashed circles. Red lines represent EPSC and blue lines represent IPSC. The black circle shows the balanced EPSC and IPSC at MT (35 dB SPL) for neuron A. The red circle shows the MT of EPSC at 30 dB SPL and the blue circle, the MT of IPSC at 40 dB SPL.

Figure 3

Number of neurons showing identical (open bars) and different (filled bars) BF/MT (left), BF alone (middle), MT alone (right) between EPSC and IPSC.

Figure 4

Correlation of the BFs (A) and MTs (B) between the EPSC and IPSC of a single neuron. Dashed line is the diagonal. Circles on the diagonals show the identical BF or MT between EPSC and IPSC. eBF/iBF: BF of EPSC and IPSC. eMT/iMT: MT of EPSC and IPSC.