Keeping the balance - importance of balanced hippocampo--prefrontal neural activity for attention and memory

This integrative in vivo neuroscience project in rats will study brain mechanisms and potential drug treatments of cognitive deficits caused by hippocampal and prefrontal neural disinhibition (reduced inhibitory GABA function). The hippocampus and prefrontal cortex are critical for memory and attention, and imbalanced neural activity in these areas caused by neural disinhibition has been linked to cognitive deficits relevant to ageing and neuropsychiatric disorders, such as schizophrenia. Combining local microinfusions of a GABA antagonist with in vivo electrophysiology and behavioural testing in rats, we recently showed that hippocampal and prefrontal neural disinhibition causes aberrant neuron firing in the disinhibited area and attentional and memory deficits (Pezze et al., 2014, J Neurosci; McGarrity et al., submitted).
Building on this research, the project has the following aims: (1) We aim to examine pharmacological mechanisms to rebalance aberrant hippocampo-prefrontal neural activity caused by neural disinhibition and to restore and sustain cognitive function, using electrophysiological and behavioural methods in our rat models. (2) We aim to examine neurochemical pathways and neural-network mechanisms mediating the cognitive impact of hippocampo-prefrontal neural disinhibition, using in vivo microdialysis and telemetric EEG; the latter will help to develop a translational biomarker of imbalanced hippocampo-prefrontal activity. These experiments will be conducted during the placement with our industry partner.