P.117 Antipsychotic effects on the synaptic plasticity-related gene Homer1a are dependent on dose, receptor profile, timing of administration, and brain regions

Background: Antipsychotic agents modulate key molecules of the postsynaptic density (PSD), including the Homer1a gene, implicated in dendritic spine architecture. How the antipsychotic receptor profile, dose, and duration of administration may influence synaptic plasticity and the Homer1a pattern of expression is yet to be determined. Methods: In situ hybridization for Homer1a was performed on rat tissue sections from cortical and striatal regions of interest (ROI) after acute or chronic administration of three antipsychotics with divergent receptor profile: Haloperidol, asenapine, and olanzapine. Univariate and multivariate analyses of the effects of topography, treatment, dose, and duration of antipsychotic administration were performed. Results: All acute treatment regimens were found to induce a consistently higher expression of Homer1a compared to chronic ones. Haloperidol increased Homer1a expression compared to olanzapine in striatum at the acute time-point. A dose effect was also observed for acute administration of haloperidol. Conclusions: Biological effects of antipsychotics on Homer1a varied strongly depending on the combination of their receptor profile, dose, duration of administration, and throughout the different brain regions. These molecular data may have translational valence and may reflect behavioral sensitization/tolerance phenomena observed with prolonged antipsychotics.

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Duration of antipsychotic treatment and doses/receptor profile modulate early gene expression throughout rat brain regions

10.26226/morressier.5b681765b56e9b005965c2af ◽

2018 ◽

Author(s):

Camilla Avagliano

Keyword(s):

Gene Expression ◽

Rat Brain ◽

Brain Regions ◽

Early Gene ◽

Antipsychotic Treatment ◽

Early Gene Expression ◽

Rat Brain Regions ◽

Receptor Profile

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Proteolytic Remodeling of Perineuronal Nets: Effects on Synaptic Plasticity and Neuronal Population Dynamics

Neural Plasticity ◽

10.1155/2018/5735789 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

P. Lorenzo Bozzelli ◽

Seham Alaiyed ◽

Eunyoung Kim ◽

Sonia Villapol ◽

Katherine Conant

Keyword(s):

Population Dynamics ◽

Synaptic Plasticity ◽

Synaptic Input ◽

Neuronal Plasticity ◽

Population Level ◽

Gamma Oscillations ◽

Brain Regions ◽

Neuronal Population ◽

Perineuronal Nets ◽

Perineuronal Net

The perineuronal net (PNN) represents a lattice-like structure that is prominently expressed along the soma and proximal dendrites of parvalbumin- (PV-) positive interneurons in varied brain regions including the cortex and hippocampus. It is thus apposed to sites at which PV neurons receive synaptic input. Emerging evidence suggests that changes in PNN integrity may affect glutamatergic input to PV interneurons, a population that is critical for the expression of synchronous neuronal population discharges that occur with gamma oscillations and sharp-wave ripples. The present review is focused on the composition of PNNs, posttranslation modulation of PNN components by sulfation and proteolysis, PNN alterations in disease, and potential effects of PNN remodeling on neuronal plasticity at the single-cell and population level.

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Emerging Link between Alzheimer’s Disease and Homeostatic Synaptic Plasticity

Neural Plasticity ◽

10.1155/2016/7969272 ◽

2016 ◽

Vol 2016 ◽

pp. 1-19 ◽

Cited By ~ 29

Author(s):

Sung-Soo Jang ◽

Hee Jung Chung

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Synaptic Plasticity ◽

Senile Plaques ◽

Long Term Potentiation ◽

Brain Regions ◽

Synaptic Activity ◽

Homeostatic Plasticity ◽

Brain Disorder

Alzheimer’s disease (AD) is an irreversible brain disorder characterized by progressive cognitive decline and neurodegeneration of brain regions that are crucial for learning and memory. Although intracellular neurofibrillary tangles and extracellular senile plaques, composed of insoluble amyloid-β(Aβ) peptides, have been the hallmarks of postmortem AD brains, memory impairment in early AD correlates better with pathological accumulation of soluble Aβoligomers and persistent weakening of excitatory synaptic strength, which is demonstrated by inhibition of long-term potentiation, enhancement of long-term depression, and loss of synapses. However, current, approved interventions aiming to reduce Aβlevels have failed to retard disease progression; this has led to a pressing need to identify and target alternative pathogenic mechanisms of AD. Recently, it has been suggested that the disruption of Hebbian synaptic plasticity in AD is due to aberrant metaplasticity, which is a form of homeostatic plasticity that tunes the magnitude and direction of future synaptic plasticity based on previous neuronal or synaptic activity. This review examines emerging evidence for aberrant metaplasticity in AD. Putative mechanisms underlying aberrant metaplasticity in AD will also be discussed. We hope this review inspires future studies to test the extent to which these mechanisms contribute to the etiology of AD and offer therapeutic targets.

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Secretory vesicle-related gene CAPS2 knock-out mice exhibit the reduced number of hippocampal GABAergic interneuron and the impairments in synaptic plasticity and behavior

Neuroscience Research ◽

10.1016/j.neures.2009.09.737 ◽

2009 ◽

Vol 65 ◽

pp. S146

Author(s):

Yo Shinoda ◽

Emi Kinameri ◽

Asako Furuya ◽

Tetsushi Sadakata ◽

Teiichi Furuichi

Keyword(s):

Synaptic Plasticity ◽

Secretory Vesicle ◽

Gabaergic Interneuron ◽

Related Gene ◽

Knock Out ◽

Knock Out Mice ◽

And Behavior

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Synaptic Plasticity and its Modulation by Alcohol

Brain Plasticity ◽

10.3233/bpl-190089 ◽

2020 ◽

Vol 6 (1) ◽

pp. 103-111 ◽

Cited By ~ 2

Author(s):

Yosef Avchalumov ◽

Chitra D. Mandyam

Keyword(s):

Synaptic Plasticity ◽

Learning And Memory ◽

Dorsal Striatum ◽

Long Term Potentiation ◽

Brain Regions ◽

Public Health Issue ◽

Cellular Mechanisms ◽

Brain Disorder ◽

The Brain

Alcohol is one of the oldest pharmacological agents used for its sedative/hypnotic effects, and alcohol abuse and alcohol use disorder (AUD) continues to be major public health issue. AUD is strongly indicated to be a brain disorder, and the molecular and cellular mechanism/s by which alcohol produces its effects in the brain are only now beginning to be understood. In the brain, synaptic plasticity or strengthening or weakening of synapses, can be enhanced or reduced by a variety of stimulation paradigms. Synaptic plasticity is thought to be responsible for important processes involved in the cellular mechanisms of learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity, and occurs via N-methyl-D-aspartate type glutamate receptor (NMDAR or GluN) dependent and independent mechanisms. In particular, NMDARs are a major target of alcohol, and are implicated in different types of learning and memory. Therefore, understanding the effect of alcohol on synaptic plasticity and transmission mediated by glutamatergic signaling is becoming important, and this will help us understand the significant contribution of the glutamatergic system in AUD. In the first part of this review, we will briefly discuss the mechanisms underlying long term synaptic plasticity in the dorsal striatum, neocortex and the hippocampus. In the second part we will discuss how alcohol (ethanol, EtOH) can modulate long term synaptic plasticity in these three brain regions, mainly from neurophysiological and electrophysiological studies. Taken together, understanding the mechanism(s) underlying alcohol induced changes in brain function may lead to the development of more effective therapeutic agents to reduce AUDs.

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Towards simulations of long-term behavior of neural networks: Modeling synaptic plasticity of connections within and between human brain regions

Neurocomputing ◽

10.1016/j.neucom.2020.01.050 ◽

2020 ◽

Vol 416 ◽

pp. 38-44

Author(s):

Emmanouil Giannakakis ◽

Cheol E. Han ◽

Bernd Weber ◽

Frances Hutchings ◽

Marcus Kaiser

Keyword(s):

Neural Networks ◽

Synaptic Plasticity ◽

Human Brain ◽

Brain Regions ◽

Long Term Behavior

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Synaptic plasticity in the mesolimbic dopamine system

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2002.1236 ◽

2003 ◽

Vol 358 (1432) ◽

pp. 815-819 ◽

Cited By ~ 78

Author(s):

Mark J. Thomas ◽

Robert C. Malenka

Keyword(s):

Synaptic Plasticity ◽

Drugs Of Abuse ◽

Neural Circuit ◽

Long Term Potentiation ◽

Brain Regions ◽

Mesolimbic Dopamine ◽

Dopamine System ◽

Mesolimbic Dopamine System

Long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical mechanisms that contribute to the neural circuit modifications that mediate all forms of experience-dependent plasticity. It has, however, been difficult to demonstrate directly that experience causes long-lasting changes in synaptic strength and that these mediate changes in behaviour. To address these potential functional roles of LTP and LTD, we have taken advantage of the powerful in vivo effects of drugs of abuse that exert their behavioural effects in large part by acting in the nucleus accumbens (NAc) and ventral tegmental area (VTA); the two major components of the mesolimbic dopamine system. Our studies suggest that in vivo drugs of abuse such as cocaine cause long-lasting changes at excitatory synapses in the NAc and VTA owing to activation of the mechanisms that underlie LTP and LTD in these structures. Thus, administration of drugs of abuse provides a distinctive model for further investigating the mechanisms and functions of synaptic plasticity in brain regions that play important roles in the control of motivated behaviour, and one with considerable practical implications.

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Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum

Physiological Genomics ◽

10.1152/physiolgenomics.00224.2006 ◽

2008 ◽

Vol 32 (3) ◽

pp. 283-298 ◽

Cited By ~ 14

Author(s):

Christopher M. Olsen ◽

Yong Huang ◽

Shirlean Goodwin ◽

Daniel C. Ciobanu ◽

Lu Lu ◽

...

Keyword(s):

Gene Expression ◽

Synaptic Plasticity ◽

Nucleus Accumbens ◽

Signaling Pathways ◽

Microarray Analysis ◽

Dorsal Striatum ◽

Brain Regions ◽

Stria Terminalis ◽

Bed Nucleus ◽

Insight Into

To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone ( Crh), the GABA transporter ( Slc6a1), and prodynorphin ( Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.

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