Emir, U. E. | Search bioRxiv

bioRxiv2018

The hippocampus and neocortical inhibitory engrams protect against memory interference

Our experiences often overlap with each other, sharing features, stimuli or higher-order information. But despite this overlap, we are able to selectively recall individual memories to guide our decisions and future actions. The neural mechanisms that support such precise memory recall, however, remain unclear. Here, using ultra-high field 7T MRI we reveal two distinct mechanisms that protect memories from interference. The first mechanism involves the hippocampus, where the BOLD signal predicts behavioural measures of memory interference, and contextual representations that aid separation of overlapping memories are organised using a relational code. The second mechanism involves neocortical inhibition: when we reduce the concentration of neocortical GABA using trans-cranial direct current stimulation (tDCS) neocortical memory interference increases in proportion to the reduction in GABA, which in turn predicts behavioural performance. Together these findings suggest that memory interference is mediated by both the hippocampus and neocortex, where the hippocampus aids separation of memories by coding context-dependent relational information, while neocortical inhibition prevents unwanted co-activation between overlapping memories.

neuroscience↗

bioRxiv2018

The dynamics of cortical GABA in human motor learning

The ability to learn novel motor skills is both a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7T MR Spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, baseline M1 GABA was strongly predictive of the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.\n\nFunding informationJ.K.:Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (204696/Z/16/Z). C.J.S.: Wellcome Trust/Royal Society Henry Dale Fellowships (102584/Z/13/Z).

neuroscience↗