Associative Learning Drives the Formation of Silent Synapses in Neuronal Ensembles of the Nucleus Accumbens

AbstractPair bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct neuronal ensembles in this region recruited during approach to either a partner or novel vole. The partner-approach neuronal ensemble increased in size following bond formation and differences in the size of approach ensembles for partner and novel voles predicts bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength indicating that ensemble plasticity is specific to partner approach. Further, the neurons comprising partner and novel approach ensembles are non-overlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner approach ensemble and its expansion upon bond formation make it a potential key substrate underlying bond formation and maturation.HighlightsWe performed in vivo Ca2+ in the nucleus accumbens of pair bonded prairie volesOverall nucleus accumbens activity did not differ during partner versus stranger interactionDistinct approach neurons exist for the partner and for the strangerPartner-approach ensemble increases as partner preference emergesWe identify a putative neuronal substrate underlying bond formation and maturation

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Neuronal mechanisms mediating pathological reward-related behaviors: A focus on silent synapses in the nucleus accumbens

Pharmacological Research ◽

10.1016/j.phrs.2018.08.025 ◽

2018 ◽

Vol 136 ◽

pp. 90-96 ◽

Cited By ~ 9

Author(s):

Dillon S. McDevitt ◽

Nicholas M. Graziane

Keyword(s):

Nucleus Accumbens ◽

Silent Synapses ◽

Neuronal Mechanisms

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Role of Nucleus Accumbens Shell Neuronal Ensembles in Context-Induced Reinstatement of Cocaine-Seeking

Journal of Neuroscience ◽

10.1523/jneurosci.0238-14.2014 ◽

2014 ◽

Vol 34 (22) ◽

pp. 7437-7446 ◽

Cited By ~ 70

Author(s):

F. C. Cruz ◽

K. R. Babin ◽

R. M. Leao ◽

E. M. Goldart ◽

J. M. Bossert ◽

...

Keyword(s):

Nucleus Accumbens ◽

Nucleus Accumbens Shell ◽

Neuronal Ensembles ◽

Cocaine Seeking

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The nucleus accumbens as a complex of functionally distinct neuronal ensembles: An integration of behavioural, electrophysiological and anatomical data

Progress in Neurobiology ◽

10.1016/0301-0082(94)90025-6 ◽

1994 ◽

Vol 42 (6) ◽

pp. 719-761 ◽

Cited By ~ 540

Author(s):

C PENNARTZ ◽

H GROENEWEGEN ◽

F LOPESDASILVA

Keyword(s):

Nucleus Accumbens ◽

Neuronal Ensembles ◽

Anatomical Data

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Dopamine D2R upregulation in nucleus accumbens indirect pathway does not affect Pavlovian or Go/No-Go Learning

10.1101/2020.04.28.066670 ◽

2020 ◽

Author(s):

Kelly Martyniuk ◽

Michelle Dandeneau ◽

Peter Balsam ◽

Christoph Kellendonk

Keyword(s):

Nucleus Accumbens ◽

Associative Learning ◽

Ventral Striatum ◽

Cost Benefit ◽

Learning Task ◽

Incentive Motivation ◽

Indirect Pathway ◽

D1 And D2 Receptors ◽

Pathway Function ◽

Pavlovian Learning

AbstractVentral striatal dopamine is thought to be important for associative learning. Dopamine exerts its role via activation of dopamine D1 and D2 receptors in the ventral striatum. Upregulation of dopamine D2R in the indirect pathway of the nucleus accumbens (NAc) impairs incentive motivation via inhibiting synaptic transmission to the ventral pallidum. Here, we determined whether upregulation of D2Rs and the resulting impairment in indirect pathway function modulates associative learning in an auditory Pavlovian reward learning task as well as Go/No-Go learning in an operant based reward driven Go/No-Go task. We found that upregulation of D2Rs in indirect pathway neurons of the NAc did not affect Pavlovian learning or the extinction of Pavlovian responses, and neither did it alter No-Go learning. A delay in the Go component of the task however could indicate a deficit in learning though it may be attributed to locomotor hyperactivity of the mice. In combination with previously published findings our data suggest that D2Rs in the NAc core play a specific role in regulating motivation by balancing cost/benefit computations but do not necessarily affect associative learning.

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Cocaine Triggers Glial-Mediated Synaptogenesis

10.1101/2020.01.20.896233 ◽

2020 ◽

Cited By ~ 2

Author(s):

Junshi Wang ◽

King-Lun Li ◽

Avani Shukla ◽

Ania Beroun ◽

Masago Ishikawa ◽

...

Keyword(s):

Nucleus Accumbens ◽

Ampa Receptor ◽

Self Administration ◽

Glutamatergic Synapses ◽

Cocaine Administration ◽

Silent Synapses ◽

Memory Traces ◽

Cocaine Seeking ◽

Silent Synapse ◽

Neuronal Receptor

AbstractSynaptogenesis is essential in forming new neurocircuits during development, and this is mediated in part by astrocyte-released thrombospondins (TSPs) and activation of their neuronal receptor, α2δ-1. Here, we show that this developmental synaptogenic mechanism is utilized during cocaine experience to induce spinogenesis and the generation of AMPA receptor-silent glutamatergic synapses in the adult nucleus accumbens (NAc). Specifically, cocaine administration activates NAc astrocytes, and preventing this activation blocks cocaine-induced generation of silent synapses. Furthermore, knockout of TSP2, or pharmacological inhibition or viral-mediated knockdown of α2δ-1, prevents cocaine-induced generation of silent synapses. Moreover, disrupting TSP2-α2δ-1-mediated spinogenesis and silent synapse generation in the NAc occludes cue-induced cocaine seeking after withdrawal from cocaine self-administration and cue-induced reinstatement of cocaine seeking after drug extinction. These results establish that silent synapses are generated by an astrocyte-mediated synaptogenic mechanism in response to cocaine experience and embed critical cue-associated memory traces that promote cocaine relapse.

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