"The hippocampal indexing theory: impact of hippocampal-neocortical backprojections on neocortical neurodynamics, plasticity and coding"

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The hippocampal formation (HF) is the highest level of association cortex. Without a functioning HF, the neocortex (NC) is severely impaired in forming or retrieving memories for specific events or extracting generalized knowledge from these memories. Although the HF is among the best understood brain systems in terms of its cell and molecular biology, synaptic plasticity, neural dynamics and coding processes, very little is known about the impact of HF outflow on the NC. The central theme and long-term goal of this research programme is to elucidate how HF back-projections actually affect NC dynamics and information storage and retrieval. To accomplish this, we will take advantage of some of the most advanced genetic, molecular, optical and electronic technologies in the toolkit of modern neuroscience, in combination with the key anatomical fact that HF-NC back-projections are almost exclusively unilateral. This unilaterality, plus the fact that unilateral HF lesions in young adult rodents do not result in severe behavioural impairments, enables powerful, within-subject experimental designs which allow comparison of neural dynamics and coding processes in NC with and (largely) without direct HF influences, in the same animal subjects. For example, unilateral HF lesions prevent NC structural changes due to enriched environments unilaterally. The objectives of this research programme include determining whether interfering with HF back-projections to NC affect 1) spatial context dependence of NC Layer II & III cells observed with experience-dependent, 2-time point, immediate-early gene (IEG) activation; 2) NC reactivation of recent activity patterns using bilateral neural ensemble recording; 3) experience-dependent changes in Layer II & III dendritic spines observed with 2-P microscopy in vivo; 4) gamma band interhemispheric coherence of local field activity; 5) global NC dynamics and sensory responsiveness using voltage-sensitive dye and cell specific Ca++ imaging. We will study the coding properties of tagged HF back-projection cells, using retrograde labelling plus IEG analysis, and of HF recipient cells, using trans-synaptic viral vector labelling plus IEG analysis and in vivo Ca++ imaging.