Modeling the Contributions of Basal Ganglia and Hippocampus to Spatial Navigation Using Reinforcement Learning

Sukumar, Deepika; Rengaswamy, Maithreye; Chakravarthy, V. Srinivasa

doi:10.1371/journal.pone.0047467

Cited by 19 publications

(14 citation statements)

References 69 publications

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“…Vagus nerve stimulation enhances extracellular hippocampal NE levels, which could be at least partly responsible for its seizure-suppressing effect in the intrahippocampal pilocarpine rat model (Raedt et al, 2011). Monoaminergic neurons and their projection fibers are not only found in the cortex, striatum and thalamus, but also in the hippocampus (Joels and Baram, 2009; Sukumar et al, 2012). In addition, monoaminergic control of neurogenesis in the adult midbrain (salamander) and hippocampus (rodents) have been suggested (Park and Enikolopov, 2010; Berg et al, 2011).…”

Section: Slc18 Familymentioning

confidence: 99%

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Liefferinge¹,

Massie²,

Portelli³

et al. 2013

Front. Cell. Neurosci.

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The vesicular neurotransmitter transporters (VNTs) are small proteins responsible for packing synaptic vesicles with neurotransmitters thereby determining the amount of neurotransmitter released per vesicle through fusion in both neurons and glial cells. Each transporter subtype was classically seen as a specific neuronal marker of the respective nerve cells containing that particular neurotransmitter or structurally related neurotransmitters. More recently, however, it has become apparent that common neurotransmitters can also act as co-transmitters, adding complexity to neurotransmitter release and suggesting intriguing roles for VNTs therein. We will first describe the current knowledge on vesicular glutamate transporters (VGLUT1/2/3), the vesicular excitatory amino acid transporter (VEAT), the vesicular nucleotide transporter (VNUT), vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT) and the vesicular γ-aminobutyric acid (GABA) transporter (VGAT) in the brain. We will focus on evidence regarding transgenic mice with disruptions in VNTs in different models of seizures and epilepsy. We will also describe the known alterations and reorganizations in the expression levels of these VNTs in rodent models for temporal lobe epilepsy (TLE) and in human tissue resected for epilepsy surgery. Finally, we will discuss perspectives on opportunities and challenges for VNTs as targets for possible future epilepsy therapies.

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Section: Slc18 Familymentioning

confidence: 99%

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Liefferinge¹,

Massie²,

Portelli³

et al. 2013

Front. Cell. Neurosci.

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“…It is well known that coupled excitatory-inhibitory pools of neurons can exhibit rich dynamic behavior like oscillations and chaos (Borisyuk et al, 1995 ; Sinha, 1999 ). This hypothesis has inspired models simulating various BG functions ranging from action selection in continuous spaces (Krishnan et al, 2011 ), reaching movements (Magdoom et al, 2011 ), spatial navigation (Sukumar et al, 2012 ), precision grip (Gupta et al, 2013 ), and gait (Muralidharan et al, 2013 ) in normal and Parkinsonian conditions. Using a network of rate-coding neurons, Kalva et al ( 2012 ) showed that exploration emerges out of the chaotic dynamics of the STN-GPe system (Kalva et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

A spiking Basal Ganglia model of synchrony, exploration and decision making

et al. 2015

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To make an optimal decision we need to weigh all the available options, compare them with the current goal, and choose the most rewarding one. Depending on the situation an optimal decision could be to either “explore” or “exploit” or “not to take any action” for which the Basal Ganglia (BG) is considered to be a key neural substrate. In an attempt to expand this classical picture of BG function, we had earlier hypothesized that the Indirect Pathway (IP) of the BG could be the subcortical substrate for exploration. In this study we build a spiking network model to relate exploration to synchrony levels in the BG (which are a neural marker for tremor in Parkinson's disease). Key BG nuclei such as the Sub Thalamic Nucleus (STN), Globus Pallidus externus (GPe) and Globus Pallidus internus (GPi) were modeled as Izhikevich spiking neurons whereas the Striatal output was modeled as Poisson spikes. The model is cast in reinforcement learning framework with the dopamine signal representing reward prediction error. We apply the model to two decision making tasks: a binary action selection task (similar to one used by Humphries et al., 2006) and an n-armed bandit task (Bourdaud et al., 2008). The model shows that exploration levels could be controlled by STN's lateral connection strength which also influenced the synchrony levels in the STN-GPe circuit. An increase in STN's lateral strength led to a decrease in exploration which can be thought as the possible explanation for reduced exploratory levels in Parkinson's patients. Our simulations also show that on complete removal of IP, the model exhibits only Go and No-Go behaviors, thereby demonstrating the crucial role of IP in exploration. Our model provides a unified account for synchronization, action section, and explorative behavior.

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“…After DA diffuses across the junction and binds with receptors expressed on the postsynaptic neuron, the activated receptors induce changes in the activity of the postsynaptic neuron. Recent postmortem and imaging studies have found that monoamine neurons and their projection fibers are located not only in the cortex, striatum, and thalamus but also in the hippocampus (Joels and Baram, ; Sukumar et al, ). Dopamine and serotonin (5‐HT) system dysregulation by the hippocampus has implications for the pathophysiology and treatment of mental or affective disorders (Grace, ; Kobayashi et al, ; Liu et al, ).…”

Section: Introductionmentioning

confidence: 99%

Altered expression of vesicular monoamine transporter 2 in epileptic patients and experimental rats

Jiang

Cao

et al. 2013

Synapse

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In the central nervous system (CNS), vesicular monoamine transporter 2 (VMAT2) transports cytoplasmic monoamines such as dopamine into synaptic vesicles for storage and subsequent exocytotic release. Recent studies have provided direct evidence for VMAT2-regulated monoamine neurotransmitter involvement in the neurophysiological activities of neurological disease. This study investigated the expression pattern of VMAT2 in patients with temporal lobe epilepsy (TLE) and in a rat model of epilepsy. We assessed the expression of VMAT2 in the temporal neocortex in 24 TLE patients using western blotting and quantitative real time PCR (qRT-PCR) analyses. These results showed that VMAT2 expression dynamically decreased in TLE patients when compared with the control subjects (n = 12). And that VMAT2 protein transiently increased in acute stages (1 day and 3 days) after epileptic seizures in pilocarpine-treated rats; however, it clearly decreased after spontaneous recurrent seizures (7 days, 21 days, and 60 days after seizures). In addition, double immunofluorescence and immunohistochemical labeling studies performed in patient and experimental animal tissue revealed that VMAT2 protein was mainly expressed in the cytoplasm and in the axons of neurons but not glial cells in the hippocampus and temporal lobe cortex. These data suggested that the abnormal expression of VMAT2 mRNA and protein in epileptic brain tissue may contribute to vulnerability toward epilepsy-related psychiatric disorders and cognitive impairment.

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Modeling the Contributions of Basal Ganglia and Hippocampus to Spatial Navigation Using Reinforcement Learning

Cited by 19 publications

References 69 publications

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

A spiking Basal Ganglia model of synchrony, exploration and decision making

Altered expression of vesicular monoamine transporter 2 in epileptic patients and experimental rats

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