Efferent connections of the hippocampal formation in the rat

doi:10.1016/0006-8993(77)90880-0

Brain Research

Volume 124, Issue 2, 25 March 1977, Pages 197-224

https://doi.org/10.1016/0006-8993(77)90880-0 Get rights and content

Abstract

In this investigation the projections of the hippocampal formation to the septal area and hypothalamus were studied in the rat with the combined use of³H-amino acid radioautography and horseradish peroxidase histochemistry.

The results indicate that all of the fibers which project to the hypothalamus and the majority of fibers which project to the septum arise from the subicular cortex and not from hippocampal pyramidal cells. The projection to both of these areas are topographically organized along the longitudinal axis of the hippocaapal formation. Specifically, fibers from subicular cortical cells situated at the septal end of the hippocampal formation which project through the medial part of the dorsal fornix terminate in the dorsomedial quadrant of the lateral septal nucleus and in the dorsal portion of the pars posterior of the medial mammillary nucleus. Fibers from progressively more posteroventral levels of the hippocampal formation which project through more lateral portions of the dorsal fornix and fimbria terminate in progressively more lateral and ventral quadrants of the lateral septal nucleus and in progressively more ventral portions of the pars posterior.

Concerning the specific origin of the fornix system, fibers from only the prosubiculum and subiculum project through both the pre- and postcommissural fornix. Hippocampal pyramidal cells from all CA fields have a restricted projection through the precommissural fornix and terminate in the caudal half of the septum while the presubiculum projects solely through the postcommissural fornix.

Reference (47)

ChronisterR.B. et al.
Post-commissural fornix. Origin and distribution in rodent
Neurosci. Lett.
(1975)
CraggB.G. et al.
Histological connections and visceral actions of the components of the fimbria in the rabbit
Exp. Neurol.
(1960)
CraggB.G. et al.
Histologic connections and electrical and autonomic responses evoked by stimulation of the dorsal fornix in the rabbit
Exp. Neurol.
(1959)
EdingerH. et al.
Single unit analysis of the hippocampal projections to the septum in the cat
Exp. Neurol.
(1973)
ElulR.
Regional differences in the hippocampus of the cat: I. Specific discharge patterns of the dorsal and ventral hippocampus and their role in generalized seizures
Electroenceph. clin. Neurophysiol.
(1964)
MeibachR.C. et al.
The efferent connections of the septal area in the rat: an analysis utilizing retrograde and anterograde transport methods
Brain Research
(1977)
SiegelA. et al.
Differential effects of electrical stimulation and lesions of the hippocampus and adjacent regions upon attack behavior in cats
Brain Research
(1968)
SiegelA. et al.
Projections of the hippocampus to the septum in the squirrel monkey
Brain Research
(1975)
StevensR. et al.
Effects of dorsal and ventral hippocampal lesions on spontaneous alteration, learned alteration and probability learning in rats
Brain Research
(1973)
AllenW.F.
Degeneration in the dog's mammillary body and Ammon's horn following transection of the fornix
J. comp. Neurol.
(1944)

AndersonC.H. et al.

Autoradiographic analysis of estradiol uptake in the brain and pituitary of the female rat

Endocrinology

(1969)

AndersonP. et al.

Organization of the hippocampal output

Exp. Brain Res.

(1973)

BrodmannK.

Vergleichende Lokalisationslehre der Grobhirnrinde

(1909)

Ca´jalS. et al.

Histologie du Systeme Nerveux de l'Homme et des Vertebres

(1911)

DeFranceJ.F. et al.

Electrophysiological analysis of the hippocampal-septal projections: 1. Response and topographical characteristics

Exp. Brain Res.

(1973)

EdingerL. et al.

Untersuchungen ueber den Fornix und des Corpus mamillare

Arch. Psychiat. Nervenkr.

(1902)

EndrocziE. et al.

The inhibitory Influence of archicortical structures on pituitary and adrenal function

Acta physiol. Acad. Sci. Hung.

(1959)

GuddenB. von

Beitrag zur Kenntniss des Corpus mamillare und der sogenannten Schenkel des Fornix

Arch. Psychiat. Nervenkr.

(1881)

GuilleryR.W.

A quantitative study of the mammillary bodies and their connexions

J. Anat. (Lond.)

(1955)

GuilleryR.W.

Degeneration in the post-commissural fornix and the mammillary peduncle of the rat

J. Anat. (Lond.)

(1956)

GurdjianE.S.

The diencephalon of the albino rat

J. comp. Neurol.

(1927)

HoneggerJ.

Comparative anatomical studies of the fornix and its relation to the conduction system in the human and mammalian brain

Rec. Zool. Suisse

(1892)

HughesK.R.

Dorsal and ventral hippocampal lesions and maze learning: influence on preoperative environment

Canad. J. Psychol.

(1965)

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: A preliminary report on this subject was presented at the Society for Neuroscience Meetings, November, 1975, and at the American Association of Anatomists Meeting, April, 1976

^**: present address: Department of Neurology, Albert Einstein College of Medicine, Bronx, N.Y. 10461 (U.S.A.).

View full text

Efferent connections of the hippocampal formation in the rat

Abstract

Neurosci. Lett.

Exp. Neurol.

Exp. Neurol.

Exp. Neurol.

Electroenceph. clin. Neurophysiol.

Brain Research

Brain Research

Brain Research

Brain Research

Degeneration in the dog's mammillary body and Ammon's horn following transection of the fornix

J. comp. Neurol.

Autoradiographic analysis of estradiol uptake in the brain and pituitary of the female rat

Endocrinology

Organization of the hippocampal output

Exp. Brain Res.

Vergleichende Lokalisationslehre der Grobhirnrinde

Histologie du Systeme Nerveux de l'Homme et des Vertebres

Electrophysiological analysis of the hippocampal-septal projections: 1. Response and topographical characteristics

Exp. Brain Res.

Untersuchungen ueber den Fornix und des Corpus mamillare

Arch. Psychiat. Nervenkr.

The inhibitory Influence of archicortical structures on pituitary and adrenal function

Acta physiol. Acad. Sci. Hung.

Beitrag zur Kenntniss des Corpus mamillare und der sogenannten Schenkel des Fornix

Arch. Psychiat. Nervenkr.

A quantitative study of the mammillary bodies and their connexions

J. Anat. (Lond.)

Degeneration in the post-commissural fornix and the mammillary peduncle of the rat

J. Anat. (Lond.)

The diencephalon of the albino rat

J. comp. Neurol.

Comparative anatomical studies of the fornix and its relation to the conduction system in the human and mammalian brain

Rec. Zool. Suisse

Dorsal and ventral hippocampal lesions and maze learning: influence on preoperative environment

Canad. J. Psychol.