Septal GABAergic neurons innervate inhibitory interneurons in the hippocampus of the macaque monkey

doi:10.1016/0306-4522(91)90334-K

Neuroscience

Volume 41, Issues 2–3, 1991, Pages 381-390

https://doi.org/10.1016/0306-4522(91)90334-K Get rights and content

Abstract

The septohippocampal projection was visualized in threeMacaca mulatta monkeys by anterograde transport ofPhaseolus vulgaris leucoagglutinin. Following injections of the lectin into the medial septal nucleus,P. vulgaris leucoagglutinin-labelled fibres were found in the hippocampal complex, mainly in stratum oriens of the CA1 subfield, throughout the CA3 subfield, and in the hilus and stratum moleculare of the dentate gyrus. The majority of labelled axons were varicose, and formed multiple contacts with cell bodies and dendrites of calbindin D_28k- and parvalbumin-immunoreactive non-pyramidal cells. GABA immunoreactivity ofP. vulgaris leucoagglutinin-labelled axons and their postsynaptic targets was investigated by sectioning varicose axon segments for correlated light and electron microscopy, and processing alternate ultrathin sections for postembedding immunogold staining for GABA. AllP. vulgaris leucoagglutinin-labelled boutons examined were GABA-immunoreactive and the majority of them formed symmetrical synapses with GABA-immunoreactive cell bodies and dendrites.

The results demonstrate that a GABAergic septohippocampal pathway exists in the monkey, and, similar to the rat, terminates on different types of GABAergic neurons, including the parvalbumin- and calbindin D_28k-containing non-pyramidal cells.

Reference (51)

ArnoldsD.E.A.T. et al.
The spectral properties of hippocampal EEG related to behavior in man
Electroenceph. clin. Neurophysiol.
(1980)
AssafS.Y. et al.
The role of a raphe serotonin system in the control of septal unit activity and hippocampal desynchronization
Neuroscience
(1978)
BaimbridgeK.G. et al.
Calcium-binding protein distribution in the rat brain
Brain Res.
(1982)
BilkeyD.K. et al.
Medial septal facilitation of hippocampal granule cell activity is mediated by inhibition of inhibitory interneurons
Brain Res.
(1985)
BlandB.H.
The physiology and pharmacology of hippocampal formation theta rhythms
Prog. Neurobiol.
(1986)
BuchanA.M.J. et al.
Distribution and co-localization of calbindin D-28k with VIP and neuropeptide Y but not somatostatin, galanin and substance P in the enteric nervous system of the rat
Peptides
(1988)
BuzsákiG.
Feed-forward inhibition in the hippocampal formation
Prog. Neurobiol.
(1984)
BuzsákiG.
Hippocampal sharp waves: their origin and significance
Brain Res.
(1986)
BuzsákiG.
Two-stage model of memory trace formation: a role for “noisy” brain states
Neuroscience
(1989)
BuzsákiG. et al.
Cellular bases of hippocampal EEG in the behaving rat
Brain Res. Rev.
(1983)

ClifferK.D. et al.

PHA-L can be transported anterogradely through fibers of passage

Brain Res.

(1988)

FantieB.D. et al.

Septal modulation of the population spike in the fascia dentata produced by perforant path stimulation in the rat

Brain Res.

(1982)

FreundT.F.

GABAergic septohippocampal neurons contain parvalbumin

Brain Res.

(1989)

GerfenC.R. et al.

An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin,Phaseolus vulgaris leucoagglutinin (PHA-L)

Brain Res.

(1984)

GulyásA.I. et al.

Innervation of different peptide-containing neurons in the hippocampus by GABAergic septal afferents

Neuroscience

(1990)

KittC.A. et al.

Fiber pathways of basal forebrain cholinergic neurons in monkeys

Brain Res.

(1987)

KosakaT. et al.

GABAergic neurons containing the Ca²⁺-binding protein parvalbumin in the rat hippocampus

Brain Res.

(1987)

KrnjevicK. et al.

Septohippocampal disinhibition

Brain Res.

(1988)

NyakasC. et al.

Detailed projection patterns of septal and diagonal band efferents to the hippocampus in the rat with emphasis on innervation of CA1 and dentate gyrus

Brain Res. Bull.

(1987)

PetscheH. et al.

The significance of the rabbit's septum as a relay station between the midbrain and the hippocampus. The control of hippocampal arousal activity by septum cells

Electroenceph. clin. Neurophysiol.

(1962)

SomogyiP. et al.

A note on the use of picric acid-paraformaldehyde-glutaraldehyde fixative for correlated light and electron microscopic immunocytochemistry

Neuroscience

(1982)

VanderwolfC.H.

Hippocampal electrical activity and voluntary movement in the rat

Electroenceph. clin. Neurophysiol.

(1969)

VanderwolfC.H. et al.

The role of serotonin in the control of cerebral activity: studies with intracerebral 5,7-dihydroxytrvptamine

Brain Res.

(1989)

WainerB.H. et al.

Cholinergic and non-cholinergic septohippocampal pathways

Neurosci. Lett.

(1985)

AmaralD.G. et al.

Subcortical afferents to the hippocampal formation in the monkey

J. comp. Neurol.

(1980)

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GABAergic neurons are well-positioned to modulate cortical circuitry, both through their direct input to cortical structures and via the highly interconnected cholinergic and GABAergic neuronal networks within the rostral basal forebrain itself (Freund and Antal, 1988; Freund and Buzsáki, 1996). Neuronal tracing studies indicate that GABAergic hippocampal interneurons are a primary target of GABAergic afferents from rostral basal forebrain (Freund and Antal, 1988; Gulyás et al., 1991). As such, an increase in the inhibitory influence from rostral basal forebrain would be expected to result in enhanced excitability of the hippocampal principal neurons.
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There are many reports that these projections modulate physiological processes classically associated with learning and memory consolidation, including long-term potentiation [6], theta rhythm [7–10], and neurogenesis [11]. According to anatomical data, the cholinergic projection terminates on all types of hippocampal cells [12], whereas septal GABAergic neurons specifically innervate hippocampal GABAergic neurons [13,14]. The septum receives midbrain dopamine innervations that originate from the ventral tegmental area (VTA), in addition both D1 and D2 class receptors are found in the septum [15–19].
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Septal GABAergic neurons innervate inhibitory interneurons in the hippocampus of the macaque monkey

Abstract

Electroenceph. clin. Neurophysiol.

Neuroscience

Brain Res.

Brain Res.

Prog. Neurobiol.

Peptides

Prog. Neurobiol.

Brain Res.

Neuroscience

Brain Res. Rev.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Neuroscience

Brain Res.

Brain Res.

Brain Res.

Brain Res. Bull.

Electroenceph. clin. Neurophysiol.

Neuroscience

Electroenceph. clin. Neurophysiol.

Brain Res.

Neurosci. Lett.

Subcortical afferents to the hippocampal formation in the monkey

J. comp. Neurol.