Gamma and theta frequency oscillations are a predominant feature of rhythmic activity in the hippocampus. We have previously demonstrated that gamma oscillations in the hippocampus may manifest as a transient (ca 1 s duration) network event or as a persistent network phenomenon. In both cases tonic network drive via activation of metabotropic glutamate or acetylcholine receptors plays a critical role in rhythmogenesis. However, the specific mechanisms involved in these two forms of network behaviour appear different. Transient episodes of gamma oscillation may occur in the absence of phasic excitatory synaptic outputs from principal cells, with large tonic depolarisations of fast-spiking interneurons alone being sufficient to elicit a gamma frequency oscillation (interneuron network gamma, ING). In contrast, persistent gamma oscillations are characterised by rhythmic trains of AMPA receptor-mediated excitatory synaptic potentials onto interneurons (pyramidal interneuron network gamma, PING). Blockade of these synaptic events leads to collapse of persistent population gamma oscillations. In each case the gamma oscillation is characterised by trains of GABAA receptor-mediated inhibitory postsynaptic potentials in principal neurons.
Here we demonstrate that, in hippocampal area CA1, a transition from gamma to theta frequency population oscillations was seen in response to metabotropic glutamate receptor activation when AMPA receptor activation was reduced. This theta frequency activity occurred in the absence of inputs from area CA3 and extra-ammonic areas and was resistant to atropine. Field theta oscillations were expressed via pyramidal distal apical dendritic burst spiking and were temporally related to trains of IPSPs with slower kinetics than those seen during gamma oscillations. Pyramidal somatic responses showed theta oscillations consisted of compound inhibitory synaptic potentials with initial IPSPs with slow kinetics followed by trains of smaller, faster IPSPs. Pharmacological modulation of IPSPs altered the theta oscillation, suggesting an inhibitory network origin. Somatic IPSPs, dendritic burst firing and stratum pyramidale interneuron activity were all temporally correlated with spiking in stratum oriens interneurons demonstrating intrinsic theta-frequency oscillations. Disruption of spiking in these interneurons abolished both field theta and theta frequency IPSP trains.
These data indicate that the magnitude of AMPA-receptor mediated excitatory synaptic responses governs the degree of gamma and theta frequency oscillations expressed in area CA1 in vitro. We suggest that low levels of AMPA-mediated drive to interneurons favours control of local network activity via slow spiking, stratum oriens interneurons (theta), whereas high levels of AMPA-mediated drive to interneurons favours control of local network activity via fast spiking, predominantly stratum radiatum interneurons (gamma). Thus factors influencing fast excitatory synaptic transmission (plasticity, neuromodulators) may consequently modify the pattern of rhythmogenesis expressed in hippocampal area CA1.
This work was funded by the MRC.