This is an historical archive of the activities of the MRC Anatomical Neuropharmacology Unit (MRC ANU) that operated at the University of Oxford from 1985 until March 2015. The MRC ANU established a reputation for world-leading research on the brain, for training new generations of scientists, and for engaging the general public in neuroscience. The successes of the MRC ANU are now built upon at the MRC Brain Network Dynamics Unit at the University of Oxford.

Spiking reduces synaptic inhibition in hippocampal neurogliaform cells

The hippocampus contains more than 20 types of inhibitory interneurons that express different proteins and impinge on different regions of pyramidal cells to regulate spatiotemporal integration of EPSPs and define temporal windows for spiking. Neurogliaform cells (NGFCs) form synapses on the distal tufts of pyramidal cell apical dendrites alongside excitatory inputs from the entorhinal cortex. NGFCs express neuronal nitric oxide synthase (nNOS), are often synaptically coupled, and fire during theta oscillations in vivo. Li et al. published a “featured article” in the Journal of Neuroscience (34(4):1280-1292, 2014) reporting a novel physiological action mediated by this interneuron type. They found that when theta-associated activity patterns were evoked in NGFCs in hippocampal slices of rat or mouse, the cells showed a transient reduction in unitary IPSP amplitude. This “firing-induced suppression of inhibition” (FSI) required back-propagation of action potentials, calcium influx through L-type calcium channels, nNOS activity, and activation of NO-sensitive guanylyl cyclase (NO-sGC) receptors, which are present on presynaptic terminals. FSI also indirectly increased the amplitude of EPSPs. Thus FSI may enhance spatial and temporal summation of excitatory inputs to NGFCs, regulating their inhibition of pyramidal cells. More in general, this work demonstrates: 1) retrograde signaling initiated by “in vivo firing pattern”, 2) interneuron back-propagation detected with fast time resolution voltage imaging, and 3) physiological role for nNOS expressed by specific interneuron types.