BASAL FOREBRAIN TOPOGRAPHY AS DEFINED BY AFFERENTS AND EFFERENTS: SEPARABLE CIRCUITS TO SUPPORT DISTINCT FUNCTIONS

Matthew Gielow, Mark Baxter, Tibor Koós, Denis, Paré, László, Záborszky, Matthew Gielow, László Záborszky
2015 unpublished
The basal forebrain (BF) is a region of heterogeneous neurons, some of which send axon terminals to the cerebral cortex. The main source of acetylcholine in the cortex arises from the cholinergic basal forebrain (BFc). Historically the BFc has been alternately described as diffuse and discrete, which has contributed to incompatible views of the system across and within scientific disciplines. The known anatomical details of the BF are not sufficient to explain the variety of functions it
more » ... functions it achieves in the cortex. This thesis describes three experiments that further investigate the anatomical details of BF cell topography, outputs, and inputs in the rat. The first utilizes retrograde tracing to show that cells projecting to visual and motor cortices are mostly found in the anterior diagonal bands and posterior basal forebrain, respectively. The BF topography of these two projection populations partially overlaps. There is also a segregation and overlap based on neurotransmitter content. The second experiment queries the BF topography of local afferents to BFc cells via monosynaptic viral tracing in ChAT-cre transgenic rats. BFc cells do not receive afferents from fellow BF cells spread across the entire BF volume. Instead, presynaptic cells coinhabit smaller pockets in which iii their postsynaptic cholinergic targets are found, suggesting the potential for modular control of portions of the BFc at the local level. The final study describes the inputs to BFc cells on the basis of their outputs to four different cortical targets utilizing the same viral tracer as above. It is possible to infect transgenic basalocortical cells via monosynaptic tracing vector injection in the cortex, at the site of axon terminals, thereby only labeling transynaptically those afferents contacting corticopetal BFc cells projecting to a particular cortical region. Subpopulations of basal forebrain cholinergic cells, that send their efferents to different cortical areas, did not receive homogeneous input, but rather received differing complements of synaptic inputs. The connectivity described herein likely serves as the anatomical basis for the differential control that the BFc exerts over its outputs. Along with this novel architecture comes a number of testable hypotheses put forth in the general discussion. iv Acknowledgements
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