We found that, in the mouse visual cortex, action potentials generated in a single layer-2/3 pyramidal (excitatory) neuron can reliably evoke large, constant-latency inhibitory postsynaptic currents in other nearby pyramidal cells. This effect is mediated by axo-axonic ionotropic glutamate receptor-mediated excitation of the nerve terminals of inhibitory interneurons, which connect to the target pyramidal cells. Therefore, individual cortical excitatory neurons can generate inhibition independently from the somatic firing of inhibitory interneurons.

We performed a systematic analysis of phase locking in pairs of electrically coupled neocortical fast-spiking (FS) and low-threshold-spiking (LTS) interneurons and in a conductance-based model of a pair of FS cells. Phase–response curves (PRCs) were obtained for real interneurons and the model cells. We used PRCs and the theory of weakly coupled oscillators to make predictions about phase-locking characteristics of cell pairs. Phase locking and the robustness of phase-locked states to differences in intrinsic frequencies of cells were directly examined by driving interneuron pairs through a wide range of firing frequencies. Calculations using PRCs accurately predicted that electrical coupling robustly synchronized the firing of interneurons over all frequencies studied (FS, 25–80 Hz; LTS, 10–30 Hz). The synchronizing ability of electrical coupling and the robustness of the phase-locked states were directly dependent on the strength of coupling but not on firing frequency. The FS cell model also predicted the existence of stable antiphase firing at frequencies below 30 Hz, but no evidence for stable antiphase firing was found using the experimentally determined PRCs or in direct measures of phase locking in pairs of interneurons. Despite significant differences in biophysical properties of FS and LTS cells, their phase-locking behavior was remarkably similar. The wide spikes and shallow action potential afterhyperpolarizations of interneurons, compared with the model, prohibited antiphase behavior. Electrical coupling between cortical interneurons of the same type maintained robust synchronous firing of cell pairs for up to 10% heterogeneity in their intrinsic frequencies.

In vivo studies suggest that precise firing of neurons is important for correct sensory representation. Principal neocortical neurons fire imprecisely when repeatedly activated by fixed sensory stimuli or current depolarizations. Here we show that in contrast to pyramidal neurons, firing in neocortical GABAergic fast-spiking (FS) interneurons is quite precise. FS interneurons are self-innervated by powerful GABAergic autaptic connections reliably activated after each spike, suggesting that autapses strongly regulate FS-cell spike timing. Indeed, blockade of autaptic transmission degraded temporal precision in multiple ways. Under these conditions, realistic dynamic-clamp hyperpolarizing autapses restored precision of spike timing, even in the presence of synaptic noise. Furthermore, firing precision was increased in pyramidal neurons by artificial GABAergic autaptic conductances, suggesting that tightly coupled synaptic feedback inhibition regulates spike timing in principal cells. Thus, well-timed inhibition, whether autaptic or synaptic, facilitates precise spike timing and promotes synchronized cortical network oscillations relevant to several behaviors.

Neocortical interneurons are very diverse in morphological, physiological, molecular, and developmental characteristics. Recent work is discovering strong correlations between these phenotypic features, confirming the intuition of Cajal and Lorente that distinct classes of interneurons exist, each presumably mediating a different circuit function. A paper by Butt et al. in this issue of Neuron describes correlations between the developmental origin of interneurons and their anatomical, electrophysiological, and molecular properties. An effort to standardize the nomenclature of interneurons is underway. Because different interneuron subtypes have different ontogenic origin, they could be classified based on their developmental specification by transcription factors.

The synchrony of neurons in extrastriate visual cortex is modulated by selective attention even when there are only small changes in firing rate (Fries, Reynolds, Rorie, & Desimone, 2001). We used Hodgkin-Huxley type models of cortical neurons to investigate the mechanism by which the degree of synchrony can be modulated independently of changes in firing rates. The synchrony of local networks of model cortical interneurons interacting through GABA(A) synapses was modulated on a fast timescale by selectively activating a fraction of the interneurons. The activated interneurons became rapidly synchronized and suppressed the activity of the other neurons in the network but only if the network was in a restricted range of balanced synaptic background activity. During stronger background activity, the network did not synchronize, and for weaker background activity, the network synchronized but did not return to an asynchronous state after synchronizing. The inhibitory output of the network blocked the activity of pyramidal neurons during asynchronous network activity, and during synchronous network activity, it enhanced the impact of the stimulus-related activity of pyramidal cells on receiving cortical areas (Salinas & Sejnowski, 2001). Synchrony by competition provides a mechanism for controlling synchrony with minor alterations in rate, which could be useful for information processing. Because traditional methods such as cross-correlation and the spike field coherence require several hundred milliseconds of recordings and cannot measure rapid changes in the degree of synchrony, we introduced a new method to detect rapid changes in the degree of coincidence and precision of spike timing.