Elsevier

Neuroscience

Volume 79, Issue 4, 6 June 1997, Pages 1051-1078
Neuroscience

Cortical input to the basal forebrain

https://doi.org/10.1016/S0306-4522(97)00049-3Get rights and content

Abstract

The arborization pattern and postsynaptic targets of corticofugal axons in basal forebrain areas have been studied by the combination of anatomical tract-tracing and pre- and postembedding immunocytochemistry. The anterograde neuronal tracer Phaseolus vulgaris leucoagglutinin was iontophoretically delivered into different neocortical (frontal, parietal, occipital), allocortical (piriform) and mesocortical (insular, prefrontal) areas in rats. To identify the transmitter phenotype in pre- or postsynaptic elements, the tracer staining was combined with immunolabeling for either glutamate or GABA, or with immunolabeling for choline acetyltransferase or parvalbumin.

Tracer injections into medial and ventral prefrontal areas gave rise to dense terminal arborizations in extended basal forebrain areas, particularly in the horizontal limb of the diagonal band and the region ventral to it. Terminals were also found to a lesser extent in the ventral part of the substantia innominata and in ventral pallidal areas adjoining ventral striatal territories. Similarly, labeled fibers from the piriform and insular cortices were found to reach lateral and ventral parts of the substantia innominata, where terminal varicosities were evident. In contrast, descending fibers from neocortical areas were smooth, devoid of terminal varicosities, and restricted to the myelinated fascicles of the internal capsule en route to more caudal targets. Ultrastructural studies obtained indicated that corticofugal axon terminals in the basal forebrain areas form synaptic contact primarily with dendritic spines or small dendritic branches (89%); the remaining axon terminals established synapses with dendritic shafts. All tracer labelled axon terminals were immunonegative for GABA, and in the cases investigated, were found to contain glutamate immunoreactivity. In material stained for the anterograde tracer and choline acetyltransferase, a total of 63 Phaseolus vulgaris leucoagglutinin varicosities closely associated with cholinergic profiles were selected for electron microscopic analysis. From this material, 37 varicosities were identified as establishing asymmetric synaptic contacts with neurons that were immunonegative for choline acetyltransferase, including spines and small dendrites (87%) or dendritic shafts (13%). Unequivocal evidence for synaptic interactions between tracer labelled terminals and cholinergic profiles could not be obtained in the remaining cases. From material stained for the anterograde tracer and parvalbumin, 40% of the labelled terminals investigated were found to establish synapses with parvalbumin-positive elements; these contacts were on dendritic shafts and were of the asymmetrical type.

The present data suggest that corticofugal axons innervate forebrain neurons that are primarily inhibitory and non-cholinergic; local forebrain axonal arborizations of these cells may represent a mechanism by which prefrontal cortical areas control basal forebrain cholinergic neurons outside the traditional boundaries of pallidal areas.

Section snippets

Animals and surgical procedures

Twelve male Sprague–Dawley rats (Zivic–Miller Laboratories, Inc., Zelienople, PA, U.S.A.; 275±25 g) were used in this study. All animals received Purina Mills Lab Chow No. 5001 and tap water ad libitum. The Rutgers University Research Animal Facility where the animals were housed, is maintained in accordance to NIH guidelines and is USDA registered and AAALAC accredited. Prior to surgery, the rats were anesthetized with sodium pentobarbital (50 mg/kg body weight). A 2.5% PHA-L (Vector Labs,

Nomenclature

For the localization of PHA-L injection sites in Fig. 1 and Fig. 5 cortical divisions were labelled according to the atlas of Swanson.[82]The prefrontal cortex (PFC) is generally defined as that part of the frontal cortex that has reciprocal connection with the mediodorsal thalamic nucleus35, 50and receives dense dopaminergic input from the ventral tegmental area.[20]The parcellation of the PFC used in this paper is largely adapted from Krettek and Price.[50]Accordingly, the PFC can be

Discussion

The present study provides evidence that i) among the corticofugal projections to the basal forebrain examined, only prefrontal, piriform and insular axons terminate in extended basal forebrain areas that are associated with cholinergic projection neurons; ii) PHA-L-labelled prefrontal boutons were found to be GABA-negative, and were confirmed to contain glutamate immunoreactivity; iii) the majority of prefrontal axons form asymmetric synapses with small dendritic shafts and spines that are

Conclusion

A comparison of the present results with data regarding the cortical targets of cholinergic neurons56, 71, 73, 92suggests that cholinergic neurons in specific forebrain subterritories may ultimately be interconnected with cortical regions sending projections to the same basal forebrain regions. For example, inputs from the piriform cortex were limited mainly to the ventral MCP–HDB regions where cholinergic projection neurons to the same cortical area have been described. Similarly, afferents

Acknowledgements

Dr Lennart Heimer (University of Virginia, NIH grant 17743) is gratefully acknowledged for allowing us to use the electron microscope facilities. Support was provided for this project by USPHS grant NS 23945 (L.Z.). The antibody against parvalbumin was a generous gift from Dr K. Baimbridge (University of British Columbia).

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