In the cerebral cortex, diverse types of neurons form intricate circuits and cooperate in time for the processing and storage of information. Recent advances reveal a spatiotemporal division of labor in cortical circuits, as exemplified in the CA1 hippocampal area. In particular, distinct GABAergic (γ-aminobutyric acid-releasing) cell types subdivide the surface of pyramidal cells and act in discrete time windows, either on the same or on different subcellular compartments. They also interact with glutamatergic pyramidal cell inputs in a domain-specific manner and support synaptic temporal dynamics, network oscillations, selection of cell assemblies, and the implementation of brain states. The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior.The cerebral cortex of mammals has a large diversity of cells operating in intricate circuits. This cellular diversity endows the cerebral cortex with the capacity to perform complex biological processes such as the subjective representation and interpretation of the world, encoding and retrieval of emotionally colored memories, understanding and empathizing with other individuals, and scientifically investigating the universe (including the mind). We argue here that time is the key metric to all cortical operations. Temporal demands drive selection for computational sophistication and also drive the evolution of neuronal diversity. In turn, cellular diversity serves the temporal organization of cortical functions in the coordination of the activity of different subcellular domains of a single neuron as well as neuronal populations.The exploration of different cells started in the late 19th century, enduringly represented by Ramon y Cajal's insights into connectivity through Golgi impregnation, which revealed the processes of single neurons (1). To the embarrassment of thousands of neuroscientists trying to explain cortical events through specific circuits today, we still lack the basic knowledge of how many types of neuron exist and how cells are interconnected. The CA1 area of the * To whom correspondence should be addressed. thomas.klausberger@pharm.ox.ac.uk (T.K.); peter.somogyi@pharm.ox.ac.uk (P.S.) . Supporting Online Material

Neural-network oscillations at distinct frequencies have been implicated in the encoding, consolidation and retrieval of information in the hippocampus. Some GABA (gamma-aminobutyric acid)-containing interneurons fire phase-locked to theta oscillations (4-8 Hz) or to sharp-wave-associated ripple oscillations (120-200 Hz), which represent different behavioural states. Interneurons also entrain pyramidal cells in vitro. The large diversity of interneurons poses the question of whether they have specific roles in shaping distinct network activities in vivo. Here we report that three distinct interneuron types--basket, axo-axonic and oriens-lacunosum-moleculare cells--visualized and defined by synaptic connectivity as well as by neurochemical markers, contribute differentially to theta and ripple oscillations in anaesthetized rats. The firing patterns of individual cells of the same class are remarkably stereotyped and provide unique signatures for each class. We conclude that the diversity of interneurons, innervating distinct domains of pyramidal cells, emerged to coordinate the activity of pyramidal cells in a temporally distinct and brain-state-dependent manner.

SYNCHRONIZATION of neuronal activity is fundamental in the operation of cortical networks. With respect to an ongoing synchronized oscillation, the precise timing of action potentials is an attractive candidate mechanism for information coding. Networks of inhibitory interneurons have been proposed to have a role in entraining cortical, synchronized 40-Hz activity. Here we demonstrate that individual GABAergic interneurons can effectively phase spontaneous firing and subthreshold oscillations in hippocampal pyramidal cells at 0 frequencies (4-7 Hz). The efficiency of this entrainment is due to interaction of GABAA-receptor-mediated hyperpolarizing synaptic events with intrinsic oscillatory mechanisms tuned to this frequency range in pyramidal cells. Moreover, this GABAergic mechanism is sufficient to synchronize the firing of pyramidal cells. Thus, owing to the divergence of each GABAergic interneuron, more than a thousand pyramidal cells may share a common temporal reference established by an individual interneuron.

Fast excitatory neurotransmission in the central nervous system occurs at specialized synaptic junctions between neurons, where a high concentration of glutamate directly activates receptor channels. Low-affinity AMPA (alpha-amino-3-hydroxy-5-methyl isoxazole propionic acid) and kainate glutamate receptors are also expressed by some glial cells, including oligodendrocyte precursor cells (OPCs). However, the conditions that result in activation of glutamate receptors on these non-neuronal cells are not known. Here we report that stimulation of excitatory axons in the hippocampus elicits inward currents in OPCs that are mediated by AMPA receptors. The quantal nature of these responses and their rapid kinetics indicate that they are produced by the exocytosis of vesicles filled with glutamate directly opposite these receptors. Some of these AMPA receptors are permeable to calcium ions, providing a link between axonal activity and internal calcium levels in OPCs. Electron microscopic analysis revealed that vesicle-filled axon terminals make synaptic junctions with the processes of OPCs in both the young and adult hippocampus. These results demonstrate the existence of a rapid signalling pathway from pyramidal neurons to OPCs in the mammalian hippocampus that is mediated by excitatory, glutamatergic synapses.