Axonal theta oscillations evoke bursting in target hippocampal subregions

Local field potentials (LFPs) measured in the extracellular matrix of the brain are postulated to arise from the integration of synaptic ionic currents and spread by volume conduction. However, there is a lack of consensus on whether these spatiotemporal voltage gradients are just an epiphenomenon of spiking or if the LFPs play a functional role in information processing. To examine a potential functional role of LFPs in information processing, we developed a microfluidic device that allows neurons from the hippocampal formation to self-wire through microfluidic channels, effectively isolating the activity of single axons between subregions of the network. We recorded spontaneous theta-band activity (4-10 Hz) in these axons whose power spectra were independent of simultaneous spiking activity. A sparse set of axons from the CA3 into the CA1 had the highest theta amplitudes. Source neurons for the axonal theta were identified through cross correlation. Functionally, sparse axonal theta phase and amplitude correlated with target subregional spiking and more strongly with burst length. These results suggest that theta voltage oscillations in axons may contribute to activation of slow voltage-gated calcium channels to drive stronger synaptic release of transmitter to coordinate hippocampal activity between subregions. We propose that theta oscillations are controlled by specific ion channels distinct from those that generate spikes, a multiplex coding mechanism for inter-regional communication with implications for routing, executive control, disease states and artificial neural networks.