scholarly journals NMDA receptor-dependent plasticity in the nucleus accumbens connects reward-predictive cues to approach responses

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Mercedes Vega-Villar ◽  
Jon C. Horvitz ◽  
Saleem M. Nicola
Keyword(s):  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Nmda Receptor ◽  
Neural Mechanism ◽  
Excitatory Synapses ◽  
Conditioned Reward ◽  
Adaptive Function ◽  
Approach Behavior ◽  
Dependent Plasticity ◽  
Reward Seeking

Abstract Learning associations between environmental cues and rewards is a fundamental adaptive function. Via such learning, reward-predictive cues come to activate approach to locations where reward is available. The nucleus accumbens (NAc) is essential for cued approach behavior in trained subjects, and cue-evoked excitations in NAc neurons are critical for the expression of this behavior. Excitatory synapses within the NAc undergo synaptic plasticity that presumably contributes to cued approach acquisition, but a direct link between synaptic plasticity within the NAc and the development of cue-evoked neural activity during learning has not been established. Here we show that, with repeated cue-reward pairings, cue-evoked excitations in the NAc emerge and grow in the trials prior to the detectable expression of cued approach behavior. We demonstrate that the growth of these signals requires NMDA receptor-dependent plasticity within the NAc, revealing a neural mechanism by which the NAc participates in learning of conditioned reward-seeking behaviors.

Early events in the trafficking of N-methyl-d-aspartate (NMDA) receptors

2003 ◽  
Vol 31 (4) ◽  
pp. 885-888 ◽  
Author(s):  
R.J. Wenthold ◽  
N. Sans ◽  
S. Standley ◽  
K. Prybylowski ◽  
R.S. Petralia
Keyword(s):  
Endoplasmic Reticulum ◽  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Biosynthetic Pathway ◽  
Biological Properties ◽  
Receptor Trafficking ◽  
Excitatory Synapses ◽  
Multiple Functions ◽  
Subunit Assembly

The N-methyl-d-aspartate (NMDA) receptor plays a central role at excitatory synapses where it has been implicated in multiple functions associated with synaptic plasticity. While this receptor has been intensely studied with respect to its physiology and pharmacology, its cell-biological properties, such as subunit assembly, post-translational processing and trafficking in neurons, are only beginning to be addressed. Critical to many of the functions of the NMDA receptor are the multiple proteins with which it interacts. While these interactions have been most thoroughly studied with respect to the receptor at the synapse, the same proteins may also interact with the receptor much earlier in its biosynthetic pathway and play important roles in receptor trafficking from the endoplasmic reticulum to the synapse.

scholarly journals Calcium channel-dependent induction of long-term synaptic plasticity at excitatory Golgi cell synapses of cerebellum

2019 ◽  
Author(s):  
F. Locatelli ◽  
T. Soda ◽  
I. Montagna ◽  
S. Tritto ◽  
L. Botta ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Granular Layer ◽  
Voltage Dependence ◽  
Mossy Fiber ◽  
Excitatory Synapses ◽  
Golgi Cell ◽  
Golgi Cells ◽  
Channel Dependent

AbstractThe Golgi cells, together with granule cells and mossy fibers, form a neuronal microcircuit regulating information transfer at the cerebellum input stage. Despite theoretical predictions, little was known about long-term synaptic plasticity at Golgi cell synapses. Here we have used whole-cell patch-clamp recordings and calcium imaging to investigate long-term synaptic plasticity at excitatory synapses impinging on Golgi cells. In acute mouse cerebellar slices, mossy fiber theta-burst stimulation (TBS) could induce either long-term potentiation (LTP) or long-term depression (LTD) at mossy fiber-Golgi cell and granule cell-Golgi cell synapses. This synaptic plasticity showed a peculiar voltage-dependence, with LTD or LTP being favored when TBS induction occurred at depolarized or hyperpolarized potentials, respectively. LTP required, in addition to NMDA channels, activation of T-type Ca2+ channels, while LTD required uniquely activation of L-type Ca2+ channels. Notably, the voltage-dependence of plasticity at the mossy fiber-Golgi cell synapses was inverted with respect to pure NMDA receptor-dependent plasticity at the neighboring mossy fiber-granule cell synapse, implying that the mossy fiber presynaptic terminal can activate different induction mechanisms depending on the target cell. In aggregate, this result shows that Golgi cells show cell-specific forms of long-term plasticity at their excitatory synapses, that could play a crucial role in sculpting the response patterns of the cerebellar granular layer.Significance statementThis paper shows for the first time a novel form of Ca2+ channel-dependent synaptic plasticity at the excitatory synapses impinging on cerebellar Golgi cells. This plasticity is bidirectional and inverted with respect to NMDA receptor-dependent paradigms, with LTD and LTP being favored at depolarized and hyperpolarized potentials, respectively. Furthermore, LTP and LTD induction requires differential involvement of T-ype and L-type voltage-gated Ca2+channels rather than the NMDA receptors alone. These results, along with recent computational predictions, support the idea that Golgi cell plasticity could play a crucial role in controlling information flow through the granular layer along with cerebellar learning and memory.

scholarly journals Reduced d-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA receptor-dependent synaptic plasticity

Brain ◽  
2013 ◽  
Vol 136 (4) ◽  
pp. 1216-1230 ◽  
Author(s):  
Livia Curcio ◽  
Maria V. Podda ◽  
Lucia Leone ◽  
Roberto Piacentini ◽  
Alessia Mastrodonato ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Nmda Receptor

Stable Competitive Dynamics Emerge from Multispike Interactions in a Stochastic Model of Spike-Timing-Dependent Plasticity

2006 ◽  
Vol 18 (10) ◽  
pp. 2414-2464 ◽  
Author(s):  
Peter A. Appleby ◽  
Terry Elliott
Keyword(s):  
Synaptic Plasticity ◽  
Stochastic Model ◽  
Higher Order ◽  
Spike Timing ◽  
Competitive Dynamics ◽  
Spike Timing Dependent Plasticity ◽  
Interaction Function ◽  
Dependent Plasticity ◽  
Order Interaction ◽  
Synaptic Dynamics

In earlier work we presented a stochastic model of spike-timing-dependent plasticity (STDP) in which STDP emerges only at the level of temporal or spatial synaptic ensembles. We derived the two-spike interaction function from this model and showed that it exhibits an STDP-like form. Here, we extend this work by examining the general n-spike interaction functions that may be derived from the model. A comparison between the two-spike interaction function and the higher-order interaction functions reveals profound differences. In particular, we show that the two-spike interaction function cannot support stable, competitive synaptic plasticity, such as that seen during neuronal development, without including modifications designed specifically to stabilize its behavior. In contrast, we show that all the higher-order interaction functions exhibit a fixed-point structure consistent with the presence of competitive synaptic dynamics. This difference originates in the unification of our proposed “switch” mechanism for synaptic plasticity, coupling synaptic depression and synaptic potentiation processes together. While three or more spikes are required to probe this coupling, two spikes can never do so. We conclude that this coupling is critical to the presence of competitive dynamics and that multispike interactions are therefore vital to understanding synaptic competition.

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

Targeted disruption to NMDA receptor dependent synaptic plasticity in area CA1 of the hippocampus

2021 ◽  
pp. 113808
Author(s):  
Alejandra Arias-Cavieres ◽  
Ateh Fonteh ◽  
Carolina I. Castro-Rivera ◽  
Alfredo J. Garcia
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Targeted Disruption ◽  
Area Ca1
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