Nicotine Exposure during Adolescence Leads to Short- and Long-Term Changes in Spike Timing-Dependent Plasticity in Rat Prefrontal Cortex

Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 08/2012; 32(31):10484-93. DOI: 10.1523/JNEUROSCI.5502-11.2012
Source: PubMed

ABSTRACT Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age can compromise the normal course of prefrontal development and lead to cognitive impairments in later life. Recently, we reported that nicotine exposure during adolescence results in a short-term increase and lasting reduction in synaptic mGluR2 levels in the rat mPFC, causing attention deficits during adulthood. It is unknown how changed synaptic mGluR2 levels after adolescent nicotine exposure affect the ability of mPFC synapses to undergo long-term synaptic plasticity. Here, we addressed this question. To model nicotine exposure, adolescent (P34-P43) or adult (P60-P69) rats were treated with nicotine injections three times per day for 10 d. We found that, both during acute activation of nicotinic receptors in the adolescent mPFC as well as immediately following nicotine treatment during adolescence, long-term plasticity in response to timed presynaptic and postsynaptic activity (tLTP) was strongly reduced. In contrast, in the mPFC of adult rats 5 weeks after they received nicotine treatment during adolescence, but not during adulthood, tLTP was increased. Short- and long-term adaptation of mPFC synaptic plasticity after adolescent nicotine exposure could be explained by changed mGluR2 signaling. Blocking mGluR2s augmented tLTP, whereas activating mGluR2s reduced tLTP. Our findings suggest neuronal mechanisms by which exposure to nicotine during adolescence alters the rules for spike timing-dependent plasticity in prefrontal networks that may explain the observed deficits in cognitive performance in later life.

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Available from: Natalia A Goriounova, Aug 16, 2015
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    • "In our case, nicotine exposure, occurring during adolescence, a still plastic developmental time window (see Introduction), resulted in persistent changes due to drug-induced organizational events on specific gene pathways. These findings raise the attention of an emerging literature that describes the lasting effects of adolescent nicotine exposure on cognitive and motivational systems in preclinical and clinical reports (Dao et al. 2011; Goriounova and Mansvelder 2012). A different mechanism of regulation should be hypothesized for the expression of the BDNF, since this gene shows similar basal expression in WT and HRM in prefrontal cortex and hippocampus, in agreement with published results (Ognibene et al. 2008, Romano et al. 2013). "
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    ABSTRACT: We have recently reported nicotine-induced stimulation of reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of heterozygous reeler mice (HRM), a putative animal model for the study of symptoms relevant to major behavioral disorders. We aimed to evaluate long-term behavioral effects and brain molecular changes as a result of adaptations to nicotine exposure in the developing HRM males. Adolescent mice (pnd 37-42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking schedule. As expected, no differences in total nicotine intake between WT (wild-type) mice and HRM were found. Long-term behavioral effects and brain molecular changes, as a consequence of nicotine exposure during adolescence, were only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor cognitive performance were modulated to WT levels by subchronic exposure to nicotine during development. Furthermore, the expected reduction in the expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of HRM appeared persistently restored by nicotine. For brain-derived neurotrophic factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However, expression levels were increased by previous nicotine in brains from both genotypes. The mRNA encoding for nicotine receptor subunits (α7, β2 and α4) did not differ between genotypes and as a result of previous nicotine exposure. These findings support the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative short- and long-term effects associated with nicotine modulation.
    Psychopharmacology 12/2013; 231(8). DOI:10.1007/s00213-013-3388-y · 3.99 Impact Factor
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    • "However, when LTP was assessed following a 5-week withdrawal period (after P78), nicotine preexposed rats exhibited enhanced LTP compared to saline-treated controls. These short-and long-term adaptations, which were both linked to impairments in mGluR2 signaling in the mPFC, were not present in rats exposed to nicotine from P60 to P69 (Goriounova and Mansvelder, 2012). "
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    ABSTRACT: Adolescence is a period of significant neurobiological change that occurs as individuals transition from childhood to adulthood. Because the nervous system is in a relatively labile state during this stage of development, it may be especially sensitive to experience-induced plasticity. One such experience that is relatively common to adolescents is the exposure to drugs of abuse, particularly alcohol and psychostimulants. In this review, we highlight recent findings on the long-lasting effects of exposure to these drugs during adolescence in humans as well as in animal models. Whenever possible, our focus is on studies that use comparison groups of adolescent- and adult-exposed subjects as this is a more direct test of the hypothesis that adolescence represents a period of enhanced vulnerability to the effects of drug-induced plasticity. Lastly, we suggest areas of future investigation that are needed and methodological concerns that should be addressed.
    Neuroscience 05/2013; 249. DOI:10.1016/j.neuroscience.2013.05.026 · 3.33 Impact Factor
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    • "Thus, increases in functional nAChR on inhibitory neurons and increased nicotine-stimulated excitation in deep layers of the PFC may be counteracted by reduced excitatory synaptic activity mediated by increased mGluR2 activity. Blocking mGluR2s with MPPG restored spike-timing-dependent potentiation following nicotine exposure during adolescence back to levels observed in animals that received saline treatment during adolescence (Goriounova and Mansvelder, 2012). This suggests that the upregulation of presynaptic mGluR2s after nicotine exposure during adolescence alters the rules for STDP in PFC networks. "
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    ABSTRACT: The majority of adolescents report to have smoked a cigarette at least once. Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age may compromise the normal course of prefrontal development and lead to cognitive impairments in later life. In addition, adolescent smokers suffer from attention deficits, which progress with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and underlie the lasting effects on cognitive function. In particular, the expression and function of metabotropic glutamate receptors (mGluRs) are changed and this has an impact on short- and long-term plasticity of glutamatergic synapses in the PFC and ultimately on the attention performance. Here, we review and discuss these recent findings.
    Frontiers in Synaptic Neuroscience 08/2012; 4:3. DOI:10.3389/fnsyn.2012.00003
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