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

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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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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Short-term synaptic plasticity expands the operational range of long-term synaptic changes in neural networks

Neural Networks ◽

10.1016/j.neunet.2019.06.002 ◽

2019 ◽

Vol 118 ◽

pp. 140-147 ◽

Cited By ~ 1

Author(s):

Guanxiong Zeng ◽

Xuhui Huang ◽

Tianzi Jiang ◽

Shan Yu

Keyword(s):

Neural Networks ◽

Synaptic Plasticity ◽

Short Term ◽

Synaptic Changes ◽

Operational Range

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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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Long-Term Behavior of Neural Networks

Relaxation in Complex Systems and Related Topics - NATO ASI Series ◽

10.1007/978-1-4899-2136-9_28 ◽

1990 ◽

pp. 205-214

Author(s):

John W. Clark

Keyword(s):

Neural Networks ◽

Long Term Behavior

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Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting

International Journal of Molecular Sciences ◽

10.3390/ijms22041916 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1916

Author(s):

Federica Campanelli ◽

Daniela Laricchiuta ◽

Giuseppina Natale ◽

Gioia Marino ◽

Valeria Calabrese ◽

...

Keyword(s):

Synaptic Plasticity ◽

Food Deprivation ◽

Physiological State ◽

Dorsal Striatum ◽

Brain Regions ◽

Synaptic Activity ◽

Striatal Neurons ◽

Long Term Effects ◽

Salient Event

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Despite an increasing number of studies pointing towards specific changes in response to dietary restrictions in brain regions, such as the nucleus accumbens and hippocampus, none have investigated the long-term effects of such practice in the dorsal striatum. This basal ganglia nucleus is involved in habit formation and in eating behavior, especially that based on dopaminergic control of motivation for food in both humans and animals. Here, we explored whether we could retrieve long-term signs of changes in AMPARs subunit composition in dorsal striatal neurons of mice acutely deprived for 12 hours/day for two consecutive days by analyzing glutamatergic neurotransmission and the principal forms of dopamine and glutamate-dependent synaptic plasticity. Overall, our data show that a moderate food deprivation in experimental animals is a salient event mirrored by a series of neuroadaptations and suggest that dietary restriction may be determinant in shaping striatal synaptic plasticity in the physiological state.

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Emergence of Visual Center-Periphery Spatial Organization in Deep Convolutional Neural Networks

10.1101/2020.02.19.956748 ◽

2020 ◽

Author(s):

Yalda Mohsenzadeh ◽

Caitlin Mullin ◽

Benjamin Lahner ◽

Aude Oliva

Keyword(s):

Neural Networks ◽

Human Brain ◽

Convolutional Neural Networks ◽

Spatial Organization ◽

Brain Regions ◽

Deep Convolutional Neural Networks ◽

Visual Center ◽

Neural Representations ◽

Parahippocampal Cortex ◽

Cortical Regions

AbstractResearch at the intersection of computer vision and neuroscience has revealed hierarchical correspondence between layers of deep convolutional neural networks (DCNNs) and cascade of regions along human ventral visual cortex. Recently, studies have uncovered emergence of human interpretable concepts within DCNNs layers trained to identify visual objects and scenes. Here, we asked whether an artificial neural network (with convolutional structure) trained for visual categorization would demonstrate spatial correspondences with human brain regions showing central/peripheral biases. Using representational similarity analysis, we compared activations of convolutional layers of a DCNN trained for object and scene categorization with neural representations in human brain visual regions. Results reveal a brain-like topographical organization in the layers of the DCNN, such that activations of layer-units with central-bias were associated with brain regions with foveal tendencies (e.g. fusiform gyrus), and activations of layer-units with selectivity for image backgrounds were associated with cortical regions showing peripheral preference (e.g. parahippocampal cortex). The emergence of a categorical topographical correspondence between DCNNs and brain regions suggests these models are a good approximation of the perceptual representation generated by biological neural networks.

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Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

10.1101/763540 ◽

2019 ◽

Author(s):

Cleiton Lopes-Aguiar ◽

Rafael N. Ruggiero ◽

Matheus T. Rossignoli ◽

Ingrid de Miranda Esteves ◽

José Eduardo Peixoto Santos ◽

...

Keyword(s):

Prefrontal Cortex ◽

Synaptic Plasticity ◽

Animal Models ◽

Long Term Potentiation ◽

Brain Regions ◽

High Frequency Stimulation ◽

Evoked Responses ◽

Term Potentiation

ABSTRACTN-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.

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