Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence

Counotte, Danielle S.; Goriounova, Natalia A.; Li, Ka Wan; Loos, Maarten; Schors, Roel C. van der; Schetters, Dustin; Schoffelmeer, Anton N. M.; Smit, August B.; Mansvelder, Huibert D.; Pattij, Tommy; Spijker, Sabine

doi:10.1038/nn.2770

Cited by 113 publications

(137 citation statements)

References 14 publications

(21 reference statements)

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“…In order to analyze whether glutamate receptors are regulated during reconsolidation in animals receiving the US+ and retrieval (US-R), we dissected the dorsal hippocampus at 1 and 4 h post-retrieval, and analyzed the synaptic membrane fraction, including membrane-bound proteins and associated proteins 26,27 , by immunoblotting for subunits of AMPA receptors. A no-shock group experiencing retrieval (NS-R) was used to control for the specificity of an aversive-associative memory (Supplementary Fig.…”

Section: Memory Recall Induces Acute Hippocampal Ampar-endocytosismentioning

confidence: 99%

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Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear

et al. 2011

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Aversive associative memories formed by the association between a neutral conditioned stimulus (CS+) and an aversive unconditioned stimulus (US+) are progressively made permanent by a process of consolidation 1 . However upon retrieval, intervention by amnestic agents [2][3][4][5][6][7] , either prior to or immediately after retrieval, results in disruption of the previously consolidated fear memory. This suggests that a consolidated memory returns to a transient destabilized state shortly after reactivation necessitating a dynamic time-dependent process of reconsolidation in order to persist further. During this reconstruction, a memory is vulnerable to experimental intervention [8][9][10] leading to amnesia, but can also be enhanced [11][12][13] or modified on the long-term [14][15][16] , thereby updating the previous memory with new information [14][15][16][17] . In clinical terms, the bidirectional and adaptive nature of reconsolidation is ideally placed to mediate both the modification of memory strength 12 , as well as memory content 16,18 , rendering this process a promising therapeutical target to counteract the hyper-responsive fear system. In order to fully exploit reconsolidation-based therapies that adapt the content of fear memories, leading to a loss of fear response on the long term, it is crucial to elucidate the molecular underpinnings of reconsolidation, which to this date remain obscure.3 Long-lasting changes in synaptic efficacy brought about by gene transcription, protein synthesis and changes in strength of hippocampal glutamatergic synapses via AMPA receptor trafficking are believed to be the cellular substrates of learning and memory [19][20][21] . Although reconsolidation is not merely a recapitulation of the initial consolidation process 22 , it has been shown that transcription, de novo protein synthesis and synaptic protein degradation in the hippocampus are also necessary for memory remodeling after retrieval 4,7,17,[23][24][25] . Here, we investigated whether the temporal profile of reconsolidation that is hypothesized to be limited to a 6 h time window 5,8 actuates a sequential profile of defined dorsohippocampal AMPA receptor synaptic plasticity that is crucial to the synaptic remodeling that underlies subsequent fear expression (changes in memory strength) and reinterpretation of fear memory after retrieval (changes in memory content). Results Memory recall induces acute hippocampal AMPAR-endocytosisIn order to analyze whether glutamate receptors are regulated during reconsolidation in animals receiving the US+ and retrieval (US-R), we dissected the dorsal hippocampus at 1 and 4 h post-retrieval, and analyzed the synaptic membrane fraction, including membrane-bound proteins and associated proteins 26,27 , by immunoblotting for subunits of AMPA receptors. A no-shock group experiencing retrieval (NS-R) was used to control for the specificity of an aversive-associative memory (Supplementary Fig. S1). These two time points were chosen as they fall within the 6-h time window after ret...

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Section: Memory Recall Induces Acute Hippocampal Ampar-endocytosismentioning

confidence: 99%

“…Synaptic membrane fractions were isolated (pooled from two or three mice, n=4-6 pooled samples/group) on a discontinuous sucrose gradient, as described previously 26,27 . Protein concentration was measured by a Bradford assay (Biorad).…”

Section: Tissue Preparation and Immunoblotting Analysismentioning

confidence: 99%

Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear

et al. 2011

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“…In rodents, adolescent animals are more susceptible to nicotine-induced CPP than adults (Vastola et al, 2002;Belluzzi et al, 2004;Shram et al, 2006;Kota et al, 2009;Shram and Le, 2010;Brielmaier et al, 2012;Ahsan et al, 2014). Moreover, nicotine administration during, but not after adolescence, has long-lasting effects on cognitive, emotional, and addiction-related behaviors (Adriani et al, 2003(Adriani et al, , 2004Counotte et al, 2009Counotte et al, , 2011Iniguez et al, 2009). Together these data point to the conclusion that adolescent nicotine exposure has long-term effects on attention, cognition, and emotional function in adulthood (Adriani et al, 2003;Counotte et al, 2009Counotte et al, , 2011Goriounova and Mansvelder, 2012a,b).…”

Section: Nicotinementioning

confidence: 99%

“…Meanwhile, chronic nicotine exposure increases expression of a wide range of genes involved in neurotransmission, signal transduction, and synaptic architecture (Polesskaya et al, 2007), and repeated nicotine exposure leads to increased phosphorylation of ERK and CREB involved in neuroplasticity (Brunzell et al, 2003). After adolescent nicotine exposure, nAChR levels in the PFC, likely representing primarily nAChRs on GABAergic interneurons, are elevated in the short-term but return to normal by 5 weeks (Counotte et al, 2012), whereas in contrast, mGlu 2 receptors are strongly downregulated at this time point (Counotte et al, 2011). In rats, acute nicotine exposure during adolescence reduced PFC LTP in response to timed presynaptic and postsynaptic activity (tLTP) but subsequently increased this LTP in adulthood (Goriounova and Mansvelder, 2012b).…”

Section: Nicotinementioning

confidence: 99%

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

Korpi¹,

Hollander²,

Farooq

et al. 2015

Pharmacol Rev

129

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“…Among molecular alteration, early nicotine exposure determines reduced mGluR2 protein and function on presynaptic terminals of PFC glutamatergic synapses. Interestingly restoring mGluR2 activity in vivo by local infusion of a group II mGluR agonist in adult rats that received nicotine as adolescents rescued attentional disturbances (Counotte et al, 2011).…”

Section: Prefrontal Cortex Dopamine Transmission In Adolescence and Dmentioning

confidence: 99%

Role of Prefrontal Cortex Dopamine and Noradrenaline Circuitry in Addiction

Carboni¹,

Cadeddu²,

Carta³

2012

Addictions - From Pathophysiology to Treatment

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Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence

Cited by 113 publications

References 14 publications

Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear

Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

Role of Prefrontal Cortex Dopamine and Noradrenaline Circuitry in Addiction

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