Acetylcholine is vital for cognitive functions of the brain. Although its actions in the individual cell are known in some detail, its effects at the network level are poorly understood. The hippocampus, which receives a major cholinergic input from the medial septum/diagonal band, is important in memory and exhibits network activity at 40 Hz during relevant behaviours. Here we show that cholinergic activation is sufficient to induce 40-Hz network oscillations in the hippocampus in vitro. Oscillatory activity is generated spontaneously in the CA3 subfield and can persist for hours. During the oscillatory state, principal neurons fire action potentials that are phase-related to the extracellular oscillation, but each neuron fires in only a small proportion of the cycles. Both excitatory and inhibitory synaptic events participate during the network oscillation in a precise temporal pattern. These results indicate that subcortical cholinergic input can control hippocampal memory processing by inducing fast network oscillations.

Coherent network oscillations in several distinct frequency bands are seen in the hippocampus of behaving animals. To investigate how different neuronal types within this network respond to oscillatory inputs we made whole‐cell current clamp recordings from three different types of neurones in the CA1 region of rat hippocampal slices: pyramidal cells, fast‐spiking interneurones and horizontal interneurones, and recorded their response to sinusoidal inputs at physiologically relevant frequencies (1‐100 Hz). Pyramidal neurones showed firing preference to inputs at theta frequencies (range 2‐7 Hz; n= 30). They showed subthreshold resonance in the same frequency range (2‐7 Hz; mean 4.1 ± 0.4 Hz; n= 19). Interneurones differed in their firing properties. Horizontal interneurones in the stratum oriens showed firing preference to inputs at theta frequencies (range 1.5‐10 Hz; n= 10). These interneurones also showed resonance at low frequencies (range 1‐5 Hz; mean 2.4 ± 0.5 Hz; n= 7). In contrast, fast‐spiking interneurones with cell bodies in the pyramidal cell layer fired preferentially at input frequencies in the gamma band (range 30‐50 Hz; n= 10/12). These interneurones showed resonance at beta‐gamma frequencies (10‐50 Hz; mean 26 ± 5 Hz; n= 7/8). Thus, in the hippocampus, different types of neurones have distinct frequency preferences. Therefore, in the CA1 layer of the hippocampal network, a compound oscillatory input may be segregated into distinct frequency components which are processed locally by distinct types of neurones.

The biologically relevant rules of synaptic potentiation were investigated in hippocampal slices from adult rat by mimicking neuronal activity seen during learning behaviours. Synaptic efficacy was monitored in two separate afferent pathways among the Schaffer collaterals during intracellular recording of CA1 pyramidal neurones. The effects of pairing presynaptic single spikes or bursts with postsynaptic single spikes or bursts, repeated at 5 Hz (‘theta’ frequency), were compared. The pairing of ten single evoked excitatory synaptic events with ten postsynaptic single action potentials at 5 Hz, repeated twelve times, failed to induce synaptic enhancement (EPSP amplitude 95 % of baseline amplitude 20 min after pairing; n= 5). In contrast, pairing the same number of action potentials, but clustered in bursts, induced robust synaptic potentiation (EPSP amplitude 163 %; P < 0·01, Student's t test; n= 5). This potentiation was input specific, long lasting (> 1 h; n= 3) and its induction was blocked by an antagonist at NMDA receptors (20‐50 μM D(‐)‐2‐amino‐5‐phosphonopentanoic acid; EPSP amplitude 109 %; n= 6). Presynaptic bursting paired with postsynaptic single action potentials did not induce input specific synaptic change (113 % in the test input vs. 111 % in the control; n= 8). In contrast, postsynaptic bursting when paired with presynaptic single action potentials was sufficient to induce synaptic potentiation when the presynaptic activity preceded the postsynaptic activity by 10 ms (150 vs. 84 % in the control input; P < 0·01; n= 10). These results indicate that, under our conditions, postsynaptic bursting activity is necessary for associative synaptic potentiation at CA1 excitatory synapses in adult hippocampus. The existence of a distinct postsynaptic signal for induction of synaptic change calls for refinement of the common interpretation of Hebb's rule, and is likely to have important implications for our understanding of cortical network operation.

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