Anatomical Neuropharmacology Unit

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.

Axo-axonic cells and hippocampal sharp waves in vivo

21 Oct 2013
Selective GABAergic input to SATB1-immunonegative axo-axonic cells and inhibition during sharp waves in vivo. GABAergic interneurons immunoreactive for the calcium-binding protein parvalbumin (magenta) are found in the CA3 area of the hippocampus. Some express the transcription factor SATB1 (yellow; top two cells), whereas others lack detectable SATB1 immunoreactivity (bottom cell). Axo-axonic cells, which are SATB1 immunonegative interneurons, are selectively innervated by GABAergic neurons of the medial septum (cyan, anterogradely-labelled medial septal axons and boutons). In CA3 during sleep and awake immobility, sharp waves (top trace) are initiated and occur simultaneously with high-frequency 'ripples' (middle trace; 130-230 Hz). The firing of axo-axonic cells (bottom trace; action potentials from a single cell) is silenced during sharp waves.

Tim Viney and his colleagues established that GABAergic axo-axonic interneurons, which only innervate the axon initial segments of pyramidal cells, are inhibited in the CA3 area of the hippocampus during so-called sharp wave-ripple events (SWRs). These SWRs represent population bursts of pyramidal cells and are initiated in the CA3 area. Axo-axonic cells, which activate GABA-A receptors, were previously discovered by members of the MRC Unit. Pyramidal cells fire sequentially during active behaviour and these sequences are replayed in a time-compressed manner during slow wave sleep and awake consummatory behaviour; at times when hippocampo-neocortical readout and memory consolidation take place. The paper also reports a selective GABAergic input to axo-axonic cells from the medial septum, and that some GABAergic medial septal neurons are activated during SWRs. The authors hypothesize that the silencing of the axo-axonic cells during SWRs enables the pyramidal cells to discharge and replay the sequences of action potentials formed by connections when the animal was awake.

The discovery that axo-axonic cells are silenced during the replay of memory traces reveals the cellular mechanism of how withdrawal of inhibition at the strategic subcellular location, the axon initial segment of pyramidal cells, assists in memory consolidation. The results contribute to defining the chronocircuit of the brain, which is the mission of the Unit.

Viney, T.J.*, Lasztóczi, B.*, Katona, L.*, Crump, M.G.*, Tukker, J.J., Klausberger, T. & Somogyi, P. (2013) Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells in vivo. Nat. Neurosci. doi:10.1038/nn.3550.

*equal first authors.