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Basal forebrain subcortical projections

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

Abstract

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.

Keywords

Mice Anterograde Tracing Substantia innominata GABA Acetylcholine 

Abbreviations

3V

Third ventricle

AAV

Adeno-associated viral vector

ac

Anterior commissure

BF

Basal forebrain

BLA

Basolateral amygdala

BST (al)

Bed nucleus of the stria terminalis, anterolateral area

CEL

Central amygdala nucleus, lateral

CEM

Central amygdala nucleus, medial

ChAT

Choline acetyltransferase

ChR2

Channelrhodopsin-2

CM

Central medial nucleus of the thalamus

CPu

Caudate putamen

DAB

Diaminobenzidine

DMH

Dorsomedial hypothalamic nucleus

DR

Dorsal raphe

DTg

Dorsal tegmental nucleus

f

Fornix

GP

Globus pallidus

HDB

Horizontal nucleus of the diagonal band

IAM

Interanteromedial nucleus of the thalamus

ic

Internal capsule

IMD

Intermediodorsal nucleus of the thalamus

ip

Intraperitoneal

IPACm

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

IPN

Interpeduncular nucleus

LC

Locus coeruleus

LDT

Laterodorsal tegmental nucleus

LHb

Lateral habenula

LPB

Lateral parabrachial nucleus

LH

Lateral hypothalamus

LSD

Lateral septum, dorsal

LSI

Lateral septum, intermediate

LPO

Lateral preoptic area

MEA

Medial amygdala nucleus

MCPO

Magnocellular preoptic nucleus

MD

Mediodorsal nucleus of the thalamus

MHb

Medial habenula

MM

Medial mammillary nucleus

MPA

Medial preoptic area

MPB

Medial parabrachial nucleus

MPO

Medial preoptic nucleus

MRF

Medullary reticular formation

MS

Medial septum

NI

Nucleus incertus

NTS

Nucleus of the solitary tract

opt

Optic tract

PBel

Parabrachial nucleus, external lateral subnucleus

PCRt

Parvicellular reticular nucleus

PeF

Perifornical nucleus of the hypothalamus

PF

Parafascicular nucleus

PH

Posterior lateral hypothalamus

PPT

Pedunculopontine nucleus

PVH

Paraventricular nucleus of the hypothalamus

PVT

Paraventricular nucleus of the thalamus

RRF

Retrorubral field

SCN

Suprachiasmatic nucleus

scp

Superior cerebellar peduncle

SI

Substantia innominata

SNc

Substantia nigra: compact part

SNr

Substantia nigra: reticular part

st

Stria terminalis

STIA

Bed nucleus of the stria terminalis, intraamygdaloid

SUM

Supramammillary nucleus

TRN

Reticular nucleus of the thalamus

VDB

Vertical nucleus of the diagonal band

VTA

Ventral tegmental area

vPAG

Ventral periaqueductal gray

vGAT

Vesicular GABA transporter

vGluT1

Vesicular glutamate transporter, type 1

vGluT2

Vesicular glutamate transporter, type 2

vGluT3

Vesicular glutamate transporter, type 3

VMH

Ventromedial nucleus of the hypothalamus

VP

Ventral pallidum

Notes

Funding

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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