Synaptic dynamics control the timing of neuronal excitation in the activated neocortical microcircuit

Abstract

It is well established that sensory stimulation results in the activity of multiple functional columns in the neocortex. The manner in which neurones within each column are active in relation to each other is, however, not known. Multiple whole-cell recordings in activated neocortical slices from rat revealed diverse correlation profiles of excitatory synaptic input to different types of neurones. The specific correlation profile between any two neurones could be predicted by the settings of synaptic depression and facilitation at the input synapses. Simulations further showed that patterned activity is essential for synaptic dynamics to impose the temporal dispersion of excitatory input. We propose that synaptic dynamics choreograph neuronal activity within the neocortical microcircuit in a context-dependent manner.

Figure 1. Cross-correlograms were obtained from multiple simultaneous voltage recordings from various neocortical neurone types under different recording conditions

A, a cluster of six neurones, 2 pyramidal and 4 interneurones in neocortical layer V. Neurones were stained using biocytin filling through the recording patch-pipette. B, under control conditions (normal ACSF, see Methods) no discharge was observed (upper trace). When slices were activated by excitant solution (Methods) neurones discharged irregularly, displaying bursts and rate fluctuations (middle trace). When the excitant solution contained fast excitatory synaptic blockers, neurones discharged in a more regular way with lower ISI variability (bottom trace). C, simultaneously obtained subthreshold voltage recordings from two cortical neurones in activated slice conditions (left) and the resulting cross-correlogram (right, black trace). The cross-correlogram is presented in comparison to that obtained under control conditions (right, grey trace).

Figure 2. Cross-correlations between pairs of pyramidal neurones (P-P) were different from those between pyramidal neurones and interneurones (P-I)

A, simultaneous subthreshold voltage recordings obtained from two layer V pyramidal neurones (left) and cross-correlogram obtained from a 1-min-long recording (right). Note the short delays between recorded events in the two neurones, and the reflection in the peak and symmetry of the cross-correlogram. B, the same as A, in this example the recorded neurones were a layer V pyramidal and a layer V interneurone. The delays observed in some of the recorded events contribute to the longer peak delays and asymmetry in the cross-correlogram. C, example of recorded voltage traces and cross-correlogram between two layer V interneurones.

Figure 3. Cross-correlations of P-I pairs in which excitatory connections were depressing (P-I_d) had shorter peak lag and median lag values than those of P-I pairs with facilitating excitatory connections (P-I_f)

A, an action-potential train in a pyramidal neurone evokes a depressing synaptic response in an interneurone (top). Cross-correlation between a pyramidal neurone and an interneurone receiving depressing excitatory synaptic input (bottom). B, an action-potential train in a pyramidal neurone evokes a facilitating synaptic response in an interneurone (top). Cross-correlation between a pyramidal neurone and an interneurone receiving facilitating excitatory synaptic input (bottom). C, comparison of peak lag and median lag between P-P, P-I_d and P-I_f correlations. Histogram of all peak lag values of different pairs of simultaneously recorded neurones (left). Both peak lag and median lag values were significantly different for different neurone pairs (for all, P<10⁻⁵; K-S test, see Methods), as presented in the bar-graphs (right).

Figure 4. Delays in cross-correlations depend on synaptic dynamics and activity patterns

Simulated integrate-and-fire neurones received common input conveyed by synapses with different dynamics. A, simulated integrate-and-fire neurones received common-input from presynaptic neurones that discharged with alternating frequencies, similar to discharge patterns observed in experiments. B, the input was conveyed by static or dynamic synapses. When the conveying synapses were static, peak lags were small and correlograms were symmetrical, whereas when dynamic synapses were used, cross-correlograms had larger peak and median lags that depended on the dynamics. C, a series of cross-correlograms of simulated voltage traces from pairs of neurones, one of which was a pyramidal neurone and the others were interneurones receiving input by synapses with incrementally increasing facilitation (increasing facilitation time constant and decreasing depression time constant), as depicted by the arrow on the left. D, temporal lags in the cross-correlation functions depend on the discharge pattern. Cross-correlation median lags are plotted against the degree of facilitation of the synapses, as characterized by the ratio between the time-constants of facilitation and depression (F/D ratio). Median lags were longer and strongly depended on the dynamics for patterned input (black trace) than when discharge was a steady-state Poisson train (grey trace) or regular (dashed trace).