Galanin expressed in the excitatory fibers attenuates synaptic strength and generalized seizures in the piriform cortex of mice

Schlifke, Irene; Kuteeva, Eugenia; Hökfelt, Tomas; Kokaia, Mérab

doi:10.1016/j.expneurol.2006.02.124

Cited by 19 publications

(19 citation statements)

References 71 publications

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“…Galanin and neuropeptide Y are colocalized with NE in LC neurons and suppress excitatory neurotransmission (Bijak 2000;Colmers et al 1987;Pieribone et al 1998;Schlifke et al 2006;Simpson et al 1999Simpson et al , 2006. Although the present experiments did not address the degree to which LC peptide co-transmitters contribute to observed effects, increases in thalamic and cortical neural responsiveness to sensory input are contrary to the previously reported actions of galanin and neuropeptide Y.…”

Section: Neuromodulatory Mechanismscontrasting

confidence: 55%

Phasic and Tonic Patterns of Locus Coeruleus Output Differentially Modulate Sensory Network Function in the Awake Rat

Devilbiss

Waterhouse

2011

Journal of Neurophysiology

109

100

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Devilbiss DM, Waterhouse BD. Phasic and tonic patterns of locus coeruleus output differentially modulate sensory network function in the awake rat. J Neurophysiol 105: 69 -87, 2011. First published October 27, 2010 doi:10.1152/jn.00445.2010. Neurons of the nucleus locus coeruleus (LC) discharge with phasic bursts of activity superimposed on highly regular tonic discharge rates. Phasic bursts are elicited by bottom-up input mechanisms involving novel/salient sensory stimuli and top-down decision making processes; whereas tonic rates largely fluctuate according to arousal levels and behavioral states. Although it is generally believed that these two modes of activity differentially modulate information processing in LC targets, the unique role of phasic versus tonic LC output on signal processing in cells, circuits, and neural networks of waking animals is not well understood. In the current study, simultaneous recordings of individual neurons within ventral posterior medial thalamus and barrel field cortex of conscious rats provided evidence that each mode of LC output produces a unique modulatory impact on single neuron responsiveness to sensory-driven synaptic input and representations of sensory information across ensembles of simultaneously recorded cells. Each mode of LC activation specifically modulated the relationship between sensory-stimulus intensity and the subsequent responses of individual neurons and neural ensembles. Overall these results indicate that phasic versus tonic modes of LC discharge exert fundamentally different modulatory effects on target neuronal circuits within the rodent trigeminal somatosensory system. As such, each mode of LC output may differentially influence signal processing as a means of optimizing behaviorally relevant neural computations within this sensory network. Likely the ability of the LC system to differentially regulate neural responses and local circuit operations according to behavioral demands extends to other brain regions including those involved in higher cognitive functions.

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Section: Neuromodulatory Mechanismscontrasting

confidence: 55%

Phasic and Tonic Patterns of Locus Coeruleus Output Differentially Modulate Sensory Network Function in the Awake Rat

Devilbiss

Waterhouse

2011

Journal of Neurophysiology

109

100

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“…in catecholaminergic pathways, showed enhanced resistance to seizure induction [11]. Overexpression of galanin under platelet-derived growth factor B promoter (thus not confined to the catecholaminergic system) inhibited the progression of kindled seizures, and increased after-discharge threshold upon hippocampal stimulation [17,18], thus confirming the antikindling action of galanin. An elegant approach further exploring the anticonvulsant role of galanin was applied in studies which used adeno-associated virus (AAV) vector carrying the galanin gene to transfect neurons in rats in vivo.…”

Section: Galanin In Temporal Lobe Epilepsymentioning

confidence: 85%

Galanin – 25 years with a multitalented neuropeptide

Lerner

Sankar

Mazarati

2008

Cell. Mol. Life Sci.

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Neuroanatomical localization and physiological properties of galanin suggest that the peptide may be involved in the regulation of seizures. Indeed, administration of galanin receptor agonists into brain areas pertinent to the initiation and propagation of epileptic activity attenuated seizure responses under conditions of animal models of epilepsy; pharmacological blocking of galanin receptors exerted proconvulsant effects. Functional deletion of both galanin and galanin type 1 receptor genes produced transgenic mice with either spontaneous seizure phenotype, or with enhanced susceptibility to seizure stimuli. At the same time, overexpression of galanin in seizure pathways, using both transgenic and virus vector transfection techniques, hindered the epileptic process. Galanin exerts anticonvulsant effects through both type 1 and type 2 receptors, with distinct downstream signaling cascades. Several synthetic agonists of galanin receptors with optimized bioavailability have been synthesized and inhibited experimental seizures upon systemic administration, thus opening an opportunity for the development of galanin-based antiepileptic drugs.

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“…We think that the increased expression of galanin and neuropeptide W (NPW) are likely to be a protective response, because of their well-studied anti-seizure effects of these peptides. For example, overexpression of galanin in several lines of transgenic mice was shown to suppress glutaminergic transmission and reduce seizure susceptibility (Mazarati et al, 2000; Schlifke et al, 2006; Kokaia et al, 2001). Administration of galanin by intra-hippocampal injection or adenovirus mediated delivery was also protective against seizures (Haberman et al, 2003; Lin et al, 2003; Mazarati and Wasterlain, 2002; Mazarati et al, 1998; McCown, 2006).…”

Section: Discussionmentioning

confidence: 99%

Altered gene expression profile in a mouse model of SCN8A encephalopathy

Sprissler

Wagnon

Bunton-Stasyshyn

et al. 2017

Experimental Neurology

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SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures. The abundance of 50 transcripts increased more than 3-fold and 15 transcripts decreased more than 3-fold after seizures. The elevated transcripts included two anti-convulsant neuropeptides and more than a dozen genes involved in reactive astrocytosis and response to neuronal damage. There was no change in the level of transcripts encoding other voltage-gated sodium, potassium or calcium channels. Reactive astrocytosis was observed in the hippocampus of mutant mice after seizures. There is considerable overlap between the genes affected in this genetic model of epilepsy and those altered by chemically induced seizures, traumatic brain injury, ischemia, and inflammation. The data support the view that gain-of-function mutations of SCN8A lead to pathogenic alterations in brain function contributing to encephalopathy.

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Galanin expressed in the excitatory fibers attenuates synaptic strength and generalized seizures in the piriform cortex of mice

Cited by 19 publications

References 71 publications

Phasic and Tonic Patterns of Locus Coeruleus Output Differentially Modulate Sensory Network Function in the Awake Rat

Phasic and Tonic Patterns of Locus Coeruleus Output Differentially Modulate Sensory Network Function in the Awake Rat

Galanin – 25 years with a multitalented neuropeptide

Altered gene expression profile in a mouse model of SCN8A encephalopathy

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