Distribution and role of Kv3.1b in neurons in the medial septum diagonal band complex

doi:10.1016/j.neuroscience.2010.01.020

Neuroscience

Volume 166, Issue 3, 31 March 2010, Pages 952-969

https://doi.org/10.1016/j.neuroscience.2010.01.020 Get rights and content

Abstract

The medial septum diagonal band complex (MS/DB) projects via cholinergic and GABAergic pathways to the hippocampus and plays a key role in the hippocampal theta rhythm. In the MS/DB we have previously described a population of fast spiking GABAergic neurons that contain parvalbumin and mediate theta frequency activity in vitro. The Kv3.1 potassium channel is a delayed rectifier channel that plays a major role in fast spiking neurons in the CNS, and has previously been localized in the MS/DB. To determine which cell types in the MS/DB express the Kv3.1b ion channel subunit, transgenic mice in which the expression of GABAergic and glutamate markers are associated with the expression of green fluorescent protein (GFP; GAD67-GFP and VGluT2-GFP mice, respectively) were used for immunofluorescence and axonal tract tracing. Electrophysiological studies were also carried out on rat MS/DB slices to examine the role of the Kv3.1 channel in theta frequency oscillations. The results for the MS/DB were as follows: (1) cholinergic cells did not express GFP in either GAD67-GFP or VGluT2-GFP mice, and there was GAD67 immunoreactivity in GFP-positive neurons in GAD67-GFP mice and in a small proportion (6%) of GFP-positive neurons in VGluT2-GFP mice. (2) Kv3.1b immunofluorescence was associated with the somata of GABAergic neurons, especially those that contained parvalbumin, and with a minority of glutamatergic neurons, but not with cholinergic neurons, and with GABAergic axonal terminal-like processes around certain GABAergic neurons. (3) Both Kv3.1b-positive and -negative GABAergic neurons were septo-hippocampal, and there was a minor projection to hippocampus from VGluT2-GFP neurons. (4) Kainate-induced theta oscillations in the MS/DB slice were potentiated rather than inhibited by the Kv3.1 blocker 4-aminopyridine, and this agent on its own produced theta frequency oscillations in MS/DB slices that were reduced by ionotropic glutamate and GABA receptor antagonists and abolished by low extracellular calcium. These studies confirm the presence of heterogeneous populations of septo-hippocampal neurons in the MS/DB, and suggest that presence of Kv3.1 in the GABAergic neurons does not contribute to theta activity through fast spiking properties, but possibly by the regulation of transmitter release from axonal terminals.

Section snippets

Tissue preparation

Tissue preparation procedures were carried out in accordance with the UK Animals (Scientific Procedures) Act 1986 and associated guidelines, and with prior approval from the local ethical committee of the University of Leeds. Every effort was made to minimize animal suffering and to reduce the number of animals used. Neuroanatomical studies were made on perfused-fixed brains from 3-week old male Wistar rats (n=2), and from adult transgenic mice (n=10) in which the expression of VGluT2, a marker

In MS/DB neurons of the GAD67-GFP mouse, there is no overlap between GFP and cholinergic markers

In neuronal somata of the MS/DB in GAD67-GFP mice, there was a direct correspondence between GAD67 immunofluorescence and GFP fluorescence, except in the cell nucleus which expressed GFP but was devoid of GAD67 immunoreactivity (Fig. 1A). There was also a correspondence between the two labels in axon terminal-like processes, but not in GFP-positive axons, which were devoid of GAD67 immunofluorescence (Fig. 1A). The average diameter of GAD67-GFP-positive neurons in the MS/DB was 12.9±2.6 μm (n

Discussion

Previous studies have indicated that septo-hippocampal, parvalbumin-containing GABAergic neurons of the MS/DB play a major role in generation of theta oscillatory activity, and that theta oscillations can be induced by kainate in the MS/DB slice. The objective of the current study was to investigate the role of Kv3.1 in these features of the rodent MS/DB. The main results showed that Kv3.1b is absent from cholinergic neurons and is expressed largely in the GABAergic neurons that contain

Acknowledgments

This work was supported by the UK Medical Research Council (grant no. G0500823), and Grant-in Aids for Scientific Research from the MEXT, Japan (YY).

References (99)

M.H. Bassant et al.
Selective immunolesion of the basal forebrain cholinergic neurons: effects on hippocampal activity during sleep and wakefulness in the rat
Neurodegeneration
(1995)
M.R. Celio
Calbindin D-28k and parvalbumin in the rat nervous system
Neuroscience
(1990)
J. Csicsvari et al.
Mechanisms of gamma oscillations in the hippocampus of the behaving rat
Neuron
(2003)
S.A. Deuchars et al.
Properties of interneurones in the intermediolateral cell column of the rat spinal cord: role of the potassium channel subunit Kv31
Neuroscience
(2001)
G. Dragoi et al.
Temporal encoding of place sequences by hippocampal cell assemblies
Neuron
(2006)
P. Dutar et al.
Septo-hippocampal neurons in the rat: further study of their physiological and pharmacological properties
Brain Res
(1986)
P. Dutar et al.
Comparison of septo-hippocampal with basalo-cortical projection neurons in the rat: an electrophysiological approach
Neurosci Lett
(1986)
R.T. Fremeau et al.
The expression of vesicular glutamate transporters defines two classes of excitatory synapse
Neuron
(2001)
T.F. Freund
GABAergic septohippocampal neurons contain parvalbumin
Brain Res
(1989)
T.F. Freund
Interneuron diversity series: rhythm and mood in perisomatic inhibition
Trends Neurosci
(2003)

K.F. Green et al.

Hippocampal theta in rats under urethane: generators and phase relations

Electroencephalogr Clin Neurophysiol

(1979)

W.H. Griffith et al.

Electrophysiology of AChE-positive neurons in basal forebrain slices

Neurosci Lett

(1986)

Z. Henderson et al.

GABA(B) receptors in the medial septum/diagonal band slice from 16–25 day rat

Neuroscience

(2005)

H.H. Jerng et al.

Molecular physiology and modulation of somatodendritic A-type potassium channels

Mol Cell Neurosci

(2004)

J. Kiss et al.

Possible glutamatergic/aspartatergic projections to the supramammillary nucleus and their origins in the rat studied by selective [H-3]D-aspartate labeling and immunocytochemistry

Neuroscience

(2002)

J. Kiss et al.

The supramamillo-hippocampal and supramammillo-septal glutamatergic/aspartatergic projections in the rat: a combined [³H]D-aspartate autoradiographic and immunohistochemical study

Neuroscience

(2000)

J. Kiss et al.

Topographical localization of neurons containing parvalbumin and choline acetyltransferase in the medial septum-diagonal band region of the rat

Neuroscience

(1990)

J.A. Knapp et al.

Electrophysiological characteristics of non-bursting, glutamate decarboxylase messenger RNA-positive neurons of the medial septum/diagonal band nuclei of guinea-pig and rat

Neuroscience

(2000)

M.G. Lee et al.

Hippocampal theta activity following selective lesion of the septal cholinergic system

Neuroscience

(1994)

C. Leranth et al.

Intraseptal connections redefined: lack of a lateral septum to medial septum path

Brain Res

(1992)

I.D. Manns et al.

Evidence for glutamate, in addition to acetylcholine and GABA, neurotransmitter synthesis in basal forebrain neurons projecting to the entorhinal cortex

Neuroscience

(2001)

J.R. Manns et al.

Hippocampal CA1 spiking during encoding and retrieval: relation to theta phase

Neurobiol Learn Mem

(2007)

H. Markram et al.

Electrophysiological characteristics of cholinergic and non-cholinergic neurons in the rat medial septum-diagonal band complex

Brain Res

(1990)

R.T. Matthews et al.

A comparison of extracellular and intracellular recordings from medial septum/diagonal band neurons in vitro

Neuroscience

(1991)

M.M. Mesulam et al.

Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6)

Neuroscience

(1983)

N.P. Morris et al.

Parvalbumin-immunoreactive, fast-spiking neurons in the medial septum/diagonal band complex of the rat: intracellular recordings in vitro

Neuroscience

(1999)

P.Y. Risold et al.

Connections of the rat lateral septal complex

Brain Res Brain Res Rev

(1997)

M.A. Rogawski

The A-current—how ubiquitous a feature of excitable cells is it?

Trends Neurosci

(1985)

B. Rudy et al.

Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing

Trends Neurosci

(2001)

C. Sekirnjak et al.

Subcellular localization of the K+ channel subunit Kv31b in selected rat CNS neurons

Brain Res

(1997)

J.E. Sweeney et al.

Arousal-dependent properties of medial septal neurons in the unanesthetized rat

Neuroscience

(1992)

O.S. Vinogradova

Expression, control, and probable functional significance of the neuronal theta-rhythm

Prog Neurobiol

(1995)

M.P. Witter et al.

Restricted origin and distribution of projections from the lateral to the medial septal complex in rat and guinea-pig

Neurosci Lett

(1992)

J.A. Yao et al.

Modulation of 4-AP block of a mammalian A-type K-channel clone by channel gating and membrane voltage

Biophys J

(1994)

T.G.J. Allen et al.

Simultaneous release of glutamate and acetylcholine from single magnocellular “cholinergic” basal forebrain neurons

J Neurosci

(2006)

E. Apartis et al.

Loss of rhythmically bursting neurons in rat medial septum following selective lesion of septohippocampal cholinergic system

J Neurophysiol

(1998)

C. Barrenechea et al.

In vivo intracellular recordings of medial septal and diagonal band of Broca neurons: relationships with theta rhythm

Exp Brain Res

(1995)

L. Betancourt et al.

Potassium (K+) channel expression in basal forebrain cholinergic neurons

J Neurosci Res

(2000)

Z. Borhegyi et al.

The supramammillary nucleus innervates cholinergic and GABAergic neurons in the medial septum-diagonal band of Broca complex

Neuroscience

(1998)

Z. Borhegyi et al.

Phase segregation of medial septal GABAergic neurons during hippocampal theta activity

J Neurosci

(2004)

J.L. Boulland et al.

Vesicular glutamate and GABA transporters sort to distinct sets of vesicles in a population of presynaptic terminals

Cereb Cortex

(2009)

E.S. Brazhnik et al.

Intracellular recordings from medial septal neurons during hippocampal theta rhythm

Exp Brain Res

(1997)

E.S. Brazhnik et al.

Action potentials and relations to the theta rhythm of medial septal neurons in vivo

Exp Brain Res

(1999)

H.M. Brew et al.

Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse

J Neurosci

(1995)

S.Q. Cai et al.

Multiple modes of A-type potassium current regulation

Curr Pharm Des

(2007)

W.A. Coetzee et al.

Molecular diversity of K+ channels

Ann N Y Acad Sci

(1999)

L.V. Colom

Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease

J Neurochem

(2006)

L.V. Colom et al.

Characterization of medial septal glutamatergic neurons and their projection to the hippocampus

Synapse

(2005)

M.L. Dallas et al.

Localization and function of the Kv31b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii

J Physiol (Lond)

(2005)

Cited by (35)

The role of NMDA receptors of the medial septum and dorsal hippocampus on memory acquisition
2016, Pharmacology Biochemistry and Behavior
Citation Excerpt :
Although cholinergic septo-hippocampal projections have been well described, but the functional significance of the glutamatergic projection has not been demonstrated (Huh et al., 2010). It has been revealed that about 4–23% of the septo-hippocampal projection is glutamatergic (Colom et al., 2005; Henderson et al., 2010). The glutamatergic system in the MS/DB, possibly via the NMDA receptors is involved in the hippocampal-dependent learning and memory (Izquierdo et al., 1992; Ogren et al., 2008).
The glutamatergic neurons in the medial septal/diagonal band of broca (MS/DB) affect the hippocampal functions by modulating the septo-hippocampal neurons. Our study investigated the possible role of NMDA receptors of the medial septum nucleus (MS) and dorsal hippocampus (CA1) on memory acquisition in male Wistar rats. Animals were bilaterally implanted with chronic cannulae in the MS and CA1. Rats were trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency as memory retrieval. Our results indicated that pre-training intra-MS or intra-CA1 infusions of NMDA (0.125 μg/rat) and D-AP7 (0.012 μg/rat) increased and decreased memory acquisition, respectively when compared to saline control group. Also, pre-training intra-CA1 and intra-MS injection of an effect dose of D-AP7 (0.012 μg/rat) along with an effect dose of NMDA (0.125 μg/rat) impaired memory acquisition. Interestingly, pre-training intra-CA1/MS infusion of D-AP7 (0.012 μg/rat) diminished memory response produced by pre-training injection of NMDA (0.125 μg/rat) in the MS/CA1, respectively (cross injection or bilateral injection). Also, all above doses of drugs did not alter locomotor activity. These results suggest that the glutamatergic pathway between the MS and CA1 regions is involved in memory acquisition process.
Functional alpha7 nicotinic receptors are expressed on immature granule cells of the postnatal dentate gyrus
2015, Brain Research
Citation Excerpt :
The objective of the immunofluorescence experiments was to examine the distribution of α7⁎nAChR immunoreactivity in DG of rat and transgenic mouse brains in relation to various other relevant markers for developmental stages of the DG. The general procedures and controls used for the immunofluorescence were as described previously (Henderson et al., 2010). Wistar rats (n=17) and GAD67-GFP (Δneo mice) (n=9) were deeply anaesthetised with an intraperitoneal injection of urethane (12 g kg−1) or Sagatal (sodium pentobarbitone, 100 mg kg−1, Rhône Mérieux Ltd., Harlow, Essex, UK).
Neurogenesis occurs throughout life in the subgranular zone of the dentate gyrus, and postnatal-born granule cells migrate into the granule cell layer and extend axons to their target areas. The α7^⁎nicotinic receptor has been implicated in neuronal maturation during development of the brain and is abundant in interneurons of the hippocampal formation of the adult brain. Signalling through these same receptors is believed also to promote maturation and integration of adult-born granule cells in the hippocampal formation. We therefore aimed to determine whether functional α7^⁎nicotinic receptors are expressed in developing granule cells of the postnatal dentate gyrus. For these experiments we used 2–3 week-old Wistar rats, and 2–9 week old transgenic mice in which GABAergic interneurons were marked by expression of green fluorescent protein. Immunohistochemistry indicated the presence of α7^⁎nicotinic receptor subunits around granule cells close around the subgranular zone which correlated with the distribution of developmental markers for immature granule cells. Whole-cell patch clamp recording showed that a proportion of granule cells responded to puffed ACh in the presence of atropine, and that these cells possessed electrophysiological properties found in immature granule cells. The nicotinic responses were potentiated by an allosteric α7^⁎nicotinic receptor modulator, which were blocked by a specific α7^⁎nicotinic receptor antagonist and were not affected by ionotropic glutamate or GABA receptor antagonists. These results suggest the presence of functional somato-dendritic α7^⁎nicotinic receptors on immature granule cells of the postnatal dentate gyrus, consistent with studies implicating α7^⁎nicotinic receptors in dendritic maturation of dentate gyrus neurons in adult brain.
Social and environmental contexts modulate sleep deprivation-induced c-Fos activation in rats
2013, Behavioural Brain Research
People often sleep deprive themselves voluntarily for social and lifestyle reasons. Animals also appear to stay awake longer as a result of their natural curiosity to explore novel environments and interact socially with conspecifics. Although multiple arousal systems in the brain are known to act jointly to promote and maintain wakefulness, it remains unclear whether these systems are similarly engaged during voluntary vs. forced wakefulness. Using c-Fos immunohistochemistry, we compared neuronal responses in rats deprived of sleep for 2 h by gentle sensory stimulation, exploration under social isolation, or exploration with social interaction, and rats under undisturbed control conditions. In many arousal, limbic, and autonomic nuclei examined (e.g., anterior cingulate cortex and locus coeruleus), the two sleep deprivation procedures involving exploration were similarly effective, and both were more effective than sleep deprivation with sensory stimulation, in increasing the number of c-Fos immunoreactive neurons. However, some nuclei (e.g., paraventricular hypothalamic nucleus and select amygdala nuclei) were more responsive to exploration with social interaction, while others (e.g., histaminergic tuberomammillary nucleus) responded more strongly to exploration in social isolation. In the rostral basal forebrain, cholinergic and GABAergic neurons responded preferentially to exploration with social interaction, whereas resident neurons in general responded most strongly to exploration without social interaction. These results indicate that voluntary exploration with/without social interaction is more effective than forced sleep deprivation with gentle sensory stimulation for inducing c-Fos in arousal and limbic/autonomic brain regions, and suggest that these nuclei participate in different aspects of arousal during sustained voluntary wakefulness.
Disturbances of septohippocampal theta oscillations in the epileptic brain: Reasons and consequences
2013, Experimental Neurology
Citation Excerpt :
In addition, the GABAergic system matures slowly (Yu et al., 2006) and relevance of data obtained at an age of P 12–28 to adulthood should be taken with care. Field activity within the theta band was recently recorded in MSDB slices (Garner et al., 2005; Henderson et al., 2010; Lu et al., 2011). It was shown that the local septal network is able to generate theta-like oscillations in response to the bath application of kainite, an ionotropic glutamate receptor agonist, or DHPG, a metabotropic glutamate receptor agonist.
Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy, characterized by hippocampal sclerosis and memory deficits. It is well-documented that intrinsic neuronal oscillations and provided by them communications between brain structures are of importance for cognition. Epilepsy disturbs these brain rhythms and presumably therefore affects memory.
Here we review studies on cellular and systemic levels devoted to the TLE-induced disturbance of theta oscillations in the septohippocampal system. Special attention is paid to the role of damage of septal and hippocampal GABAergic cells in theta activity abnormalities. We also compare differences between native (in vivo) theta oscillations with those obtained in in vitro preparations of hippocampus and medial septum and find that in vitro they resemble epileptiform activity in some respects.
Scopolamine induced memory impairment; possible involvement of NMDA receptor mechanisms of dorsal hippocampus and/or septum
2012, Behavioural Brain Research
Citation Excerpt :
While cholinergic septo-hippocampal projections have been well described, but the functional significance of the glutamatergic projection has not been demonstrated [64]. Moreover, about 4–23% of the septo-hippocampal projection is glutamatergic [65,66]. The glutamatergic system in the MS/VDB, possibly through the NMDA receptors is involved in hippocampal-dependent learning and memory [67].
The anatomical connections of septum and hippocampus and the influence of cholinergic and glutamatergic projections in these sites have been reported. In the present study, the effect of pre-training intra-dorsal hippocampal (CA1) and intra-medial septal (MS) administration of scopolamine, a nonselective muscarinic acetylcholine antagonist, and NMDA receptor agents and their interactions, on acquisition of memory have been investigated.
The animals were bilaterally implanted with chronic cannulae in the CA1 regions and in the medial septum. Animals were trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency as memory retrieval.
Intra-CA1 or intra-MS injections of scopolamine (0.5, 1 and 2 μg/rat) and D-AP7 (a competitive NMDA receptor antagonist; 0.025, 0.05 and 0.1 μg/rat) reduced, while NMDA (0.125 and 0.25 μg/rat) increased memory. Intra-MS injection of a subthreshold dose of NMDA reduced scopolamine induced amnesia in the MS. However, similar injection of NMDA into CA1 did not alter scopolamine response when injected into CA1. Moreover, intra-MS or -CA1 injection of a subthreshold dose of NMDA did not alter scopolamine response in the CA1 or MS respectively. On the other hand, co-administration subthreshold doses of D-AP7 and scopolamine into CA1 and/or MS induced amnesia.
The cholinergic system between septum and CA1 are modulating memory acquisition processes induced by glutamatergic system in the CA1 or septum and co-activation of these systems in these sites can influence learning and memory.
The Basal Forebrain Cholinergic Projection System in Mice
2012, The Mouse Nervous System
The basal forebrain is composed of an affiliation of heterogeneous structures and includes the medial septum, ventral pallidum (VP), diagonal band nuclei, substantia innominata/extended amygdala, and peripallidal regions. The basal forebrain is located close to the medial and ventral surfaces of the cerebral hemispheres that develop from the subpallium. This highly complex brain region has been implicated in cortical activation, attention, motivation, memory, and neuropsychiatric disorders such as Alzheimer's disease Parkinson's disease, schizophrenia, and drug abuse. The basal forebrain contains a heterogeneous mixture of cell types that differ in transmitter content, morphology, and projection pattern. One of the most prominent features of the mammalian basal forebrain is the presence of a collection of aggregated and non-aggregated, large, hyperchromic neurons, many of them containing choline acetyl transferase (ChAT), the critical enzyme in the synthesis of acetylcholine (ACh); these neurons project to the cerebral cortex. Single unit studies in anesthetized and behaving rats showed that identified cholinergic neurons increase their firing during cortical EEG activation. Activity of basal forebrain cholinergic neurons is associated with an increase in cortical release of ACh. Cortical ACh release is high during wakefulness and rapid eye movement (REM) sleep and is low during non-REM sleep that is characterized by EEG delta power with periodic oscillations of medium-frequency high amplitude spindles. Against the relatively “diffuse” termination of the ascending brainstem and hypothalamic axons in the basal forebrain, the restricted input from the prefrontal cortex to basal forebrain neurons, including specific clusters, might be instrumental in communicating state-related changes from basal forebrain neurons to specific posterior sensory areas to modulate selective cognitive processes.

View all citing articles on Scopus

View full text

Systems NeuroscienceResearch PaperDistribution and role of Kv3.1b in neurons in the medial septum diagonal band complex

Abstract

Section snippets

Tissue preparation

In MS/DB neurons of the GAD67-GFP mouse, there is no overlap between GFP and cholinergic markers

Discussion

Acknowledgments

Neurodegeneration

Neuroscience

Neuron

Neuroscience

Neuron

Brain Res

Neurosci Lett

Neuron

Brain Res

Trends Neurosci

Electroencephalogr Clin Neurophysiol

Neurosci Lett

Neuroscience

Mol Cell Neurosci

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Brain Res

Neuroscience

Neurobiol Learn Mem

Brain Res

Neuroscience

Neuroscience

Neuroscience

Brain Res Brain Res Rev

Trends Neurosci

Trends Neurosci

Brain Res

Neuroscience

Prog Neurobiol

Neurosci Lett

Biophys J

Simultaneous release of glutamate and acetylcholine from single magnocellular “cholinergic” basal forebrain neurons

J Neurosci

Loss of rhythmically bursting neurons in rat medial septum following selective lesion of septohippocampal cholinergic system

J Neurophysiol

In vivo intracellular recordings of medial septal and diagonal band of Broca neurons: relationships with theta rhythm

Exp Brain Res

Potassium (K+) channel expression in basal forebrain cholinergic neurons

J Neurosci Res

The supramammillary nucleus innervates cholinergic and GABAergic neurons in the medial septum-diagonal band of Broca complex

Neuroscience

Phase segregation of medial septal GABAergic neurons during hippocampal theta activity

J Neurosci

Vesicular glutamate and GABA transporters sort to distinct sets of vesicles in a population of presynaptic terminals

Cereb Cortex

Intracellular recordings from medial septal neurons during hippocampal theta rhythm

Exp Brain Res

Action potentials and relations to the theta rhythm of medial septal neurons in vivo

Exp Brain Res

Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse

J Neurosci

Multiple modes of A-type potassium current regulation

Curr Pharm Des

Molecular diversity of K+ channels

Ann N Y Acad Sci

Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease

J Neurochem

Characterization of medial septal glutamatergic neurons and their projection to the hippocampus

Synapse

Localization and function of the Kv31b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii

J Physiol (Lond)

Systems Neuroscience
Research Paper
Distribution and role of Kv3.1b in neurons in the medial septum diagonal band complex