The roles of distinct nucleus basalis projections in cognition

Cold Spring Harbor Laboratory, Cold Spg Hbr NY

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Abstract

? DESCRIPTION (provided by applicant): Our long-term goal is to understand how the forebrain neuromodulatory region, nucleus basalis (NB) supports cognitive functions. NB is thought to play significant roles in learning and attention, and its degeneration parallels the decline of cognitive functions in patients in a range of dementias. However, identified projection cell-types have never been recorded. Our objective is to determine what information is represented in and signaled by distinct NB long- range cortical projections and establish their causal behavioral function. To study this issue, we have developed a quantitative psychophysical auditory detection task for mice, adapted from human and primate work, enabling us to assess a number of behavioral correlates of NB neurons. In addition, we will use our recently developed optogenetic toolkit to record from all the three known NB projection cell-types: cholinergic, GABAergic and glutamatergic neurons during behavior for the first time. Our central hypothesis is that NB broadcasts distinct cognitive signals in a cell-type-specific manner. First, we operationalized different cognitive variables so that the activity of every neuron encoding a particular cognitive variable can be statistically evaluated. Specifically we will assess the moment-to-moment, trial-to-trial correlations between firing rates and different behavioral measures (e.g. accuracy or reaction time, RT). Second, in each of the three aims we will consider one of the major projection systems and evaluate when they are recruited during behavior and what cognitive variables they encode. Finally, using the temporal information gleaned from these recordings we will test the causal role of different NB projection cell- types using optogenetic gain and loss of function manipulations. Upon completion of these aims, we expect to establish the cell-type specific broadcast signals from NB and their role in defined aspects of cognition.