Basal forebrain subcortical projections

  • Lindsay J. Agostinelli
  • Joel C. Geerling
  • Thomas E. ScammellEmail author
Original Article


The basal forebrain (BF) contains at least three distinct populations of neurons (cholinergic, glutamatergic, and GABA-ergic) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata). Much attention has focused on the BF’s ascending projections to cortex, but less is known about descending projections to subcortical regions. Given the neurochemical and anatomical heterogeneity of the BF, we used conditional anterograde tracing to map the patterns of subcortical projections from multiple BF regions and neurochemical cell types using mice that express Cre recombinase only in cholinergic, glutamatergic, or GABAergic neurons. We confirmed that different BF regions innervate distinct subcortical targets, with more subcortical projections arising from neurons in the caudal and lateral BF (substantia innominata and magnocellular preoptic area). Additionally, glutamatergic and GABAergic BF neurons have distinct patterns of descending projections, while cholinergic descending projections are sparse. Considering the intensity of glutamatergic and GABAergic descending projections, the BF likely acts through subcortical targets to promote arousal, motivation, and other behaviors.


Mice Anterograde Tracing Substantia innominata GABA Acetylcholine 



Third ventricle


Adeno-associated viral vector


Anterior commissure


Basal forebrain


Basolateral amygdala

BST (al)

Bed nucleus of the stria terminalis, anterolateral area


Central amygdala nucleus, lateral


Central amygdala nucleus, medial


Choline acetyltransferase




Central medial nucleus of the thalamus


Caudate putamen




Dorsomedial hypothalamic nucleus


Dorsal raphe


Dorsal tegmental nucleus




Globus pallidus


Horizontal nucleus of the diagonal band


Interanteromedial nucleus of the thalamus


Internal capsule


Intermediodorsal nucleus of the thalamus




Interstitial nucleus of the posterior limb of the anterior commissure, medial


Interpeduncular nucleus


Locus coeruleus


Laterodorsal tegmental nucleus


Lateral habenula


Lateral parabrachial nucleus


Lateral hypothalamus


Lateral septum, dorsal


Lateral septum, intermediate


Lateral preoptic area


Medial amygdala nucleus


Magnocellular preoptic nucleus


Mediodorsal nucleus of the thalamus


Medial habenula


Medial mammillary nucleus


Medial preoptic area


Medial parabrachial nucleus


Medial preoptic nucleus


Medullary reticular formation


Medial septum


Nucleus incertus


Nucleus of the solitary tract


Optic tract


Parabrachial nucleus, external lateral subnucleus


Parvicellular reticular nucleus


Perifornical nucleus of the hypothalamus


Parafascicular nucleus


Posterior lateral hypothalamus


Pedunculopontine nucleus


Paraventricular nucleus of the hypothalamus


Paraventricular nucleus of the thalamus


Retrorubral field


Suprachiasmatic nucleus


Superior cerebellar peduncle


Substantia innominata


Substantia nigra: compact part


Substantia nigra: reticular part


Stria terminalis


Bed nucleus of the stria terminalis, intraamygdaloid


Supramammillary nucleus


Reticular nucleus of the thalamus


Vertical nucleus of the diagonal band


Ventral tegmental area


Ventral periaqueductal gray


Vesicular GABA transporter


Vesicular glutamate transporter, type 1


Vesicular glutamate transporter, type 2


Vesicular glutamate transporter, type 3


Ventromedial nucleus of the hypothalamus


Ventral pallidum



NIH P01 HL095491 to TS, NIH P01 HL095491-02S1 to LJA.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lindsay J. Agostinelli
    • 1
    • 2
  • Joel C. Geerling
    • 1
    • 2
  • Thomas E. Scammell
    • 1
    Email author
  1. 1.Department of NeurologyBeth Israel Deaconess Medical Center and Harvard Medical SchoolBostonUSA
  2. 2.Department of Neurology, Roy J. and Lucille A. Carver College of MedicineUniversity of IowaIowa CityUSA

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