Neuronal assemblies in the hippocampus are central to the encoding, consolidation and retrieval of memories. The activity patterns of networks of hippocampal neurons change in association with different behaviours, and these distinct network states are proposed to contribute to specific memory processes. Inhibitory interneurons are known to synchronize pyramidal cell firing in the hippocampus. In a paper published in Nature, Klausberger and colleagues now provide evidence that the diversity of interneurons helps to shape the brain-state-dependent activity of hippocampal neural networks.

The hippocampus houses an assortment of interneurons, which can be classified on the basis of several properties, including their specific innervation of distinct domains of pyramidal cells. Klausberger et al. examined the possibility that different interneuron classes contribute differentially to network activity patterns. They made electrophysiological recordings in the CA1 region of anaesthetized rats from three types of interneuron — basket, axo-axonic and oriens–lacunosum-moleculare (O–LM) cells — which were visualized and distinguished by their patterns of synaptic connectivity and by the use of neurochemical markers. The firing patterns of these interneurons were monitored during two types of network activity: theta oscillations (4–8 Hz), which are associated with exploratory behaviour and rapid-eye-movement sleep in non-anaesthetized animals, and sharp-wave-associated ripple oscillations (120–200 Hz), which are observed during periods of inactivity and in slow-wave sleep.

The authors found that, whereas firing patterns generated by single cells of the same class were remarkably alike, serving as a unique 'signature' for each type of interneuron, the phase preferences of these classes during theta or ripple activity were markedly different. For example, during theta oscillations, basket cells fired preferentially on the descending phase of each wave, axo-axonic cells fired right after the peak of the theta wave, and O–LM cells fired rhythmically at the trough of the theta cycle. It seems likely that these three types of interneuron make specific contributions to the production of network oscillations through their characteristic patterns of activity.

Further studies are warranted to find out exactly how the precisely timed firing of these interneurons coordinates the activity of hippocampal pyramidal cells, and to extend these observations to other interneuron classes, to other network states and, importantly, to non-anaesthetized, behaving animals.