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The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens.

Ji X, Saha S, Martin GE - Front Synaptic Neurosci (2015)

Bottom Line: It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol.However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive).Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School Worcester, MA, USA.

ABSTRACT
It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive). Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD) and long-term potentiation (LTP) and long-term potentiation (tLTP) and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

No MeSH data available.


Related in: MedlinePlus

(A) Each open symbol, representing an individual MSN, indicates changes of EPSP amplitudes expressed as percent of control and measured 20 min after induction. Symbols above and below broken line show tLTP and tLTD, respectively. Change of synaptic strength after induction is expressed as percent of control (100%). Open circles, squares and diamonds indicate EPSPs amplitude following stimulation of cortical, amygdala and hippocampal afferents, respectively. Red symbols with SEM show averaged overall changes. In parentheses are shown number of neurons recorded in each condition. Solid gray symbols indicate the magnitude of tLTD recorded in nine MSNs after reversing the pairing order (i.e., EPSP followed by AP) during induction of plasticity. Note that this new pairing order has no impact on plasticity. Inset shows long-term potentiation (tLTP) and timing dependent long-term depression (tLTD) in MSNs expressing dopamine D1 receptors recorded in B6.Cg-Tg (Drd1a-tdTomato) mice. (B,C) show respectively average tLTP and tLTD expressed as percent of control following stimulation of PFCx (circle), amygdala (square) and hippocampal (diamond) inputs.
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Figure 3: (A) Each open symbol, representing an individual MSN, indicates changes of EPSP amplitudes expressed as percent of control and measured 20 min after induction. Symbols above and below broken line show tLTP and tLTD, respectively. Change of synaptic strength after induction is expressed as percent of control (100%). Open circles, squares and diamonds indicate EPSPs amplitude following stimulation of cortical, amygdala and hippocampal afferents, respectively. Red symbols with SEM show averaged overall changes. In parentheses are shown number of neurons recorded in each condition. Solid gray symbols indicate the magnitude of tLTD recorded in nine MSNs after reversing the pairing order (i.e., EPSP followed by AP) during induction of plasticity. Note that this new pairing order has no impact on plasticity. Inset shows long-term potentiation (tLTP) and timing dependent long-term depression (tLTD) in MSNs expressing dopamine D1 receptors recorded in B6.Cg-Tg (Drd1a-tdTomato) mice. (B,C) show respectively average tLTP and tLTD expressed as percent of control following stimulation of PFCx (circle), amygdala (square) and hippocampal (diamond) inputs.

Mentions: All experiments, with the exception of one where male B6.Cg-Tg (Drd1a-tdTomato) were used (inset, Figure 3A), were performed on male wild type (wt) and BK channel β4 knockout C57Bl/6J mice. All mice were handled according to the American Association for the Accreditation of Laboratory Animal Care guideline. The protocol was approved by the Institutional Animal Care and Use Committee of University of Massachusetts Medical School. Mice were maintained at constant temperature and humidity with a 12-h light–dark cycle. Water and food were provided ad libitum.


The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens.

Ji X, Saha S, Martin GE - Front Synaptic Neurosci (2015)

(A) Each open symbol, representing an individual MSN, indicates changes of EPSP amplitudes expressed as percent of control and measured 20 min after induction. Symbols above and below broken line show tLTP and tLTD, respectively. Change of synaptic strength after induction is expressed as percent of control (100%). Open circles, squares and diamonds indicate EPSPs amplitude following stimulation of cortical, amygdala and hippocampal afferents, respectively. Red symbols with SEM show averaged overall changes. In parentheses are shown number of neurons recorded in each condition. Solid gray symbols indicate the magnitude of tLTD recorded in nine MSNs after reversing the pairing order (i.e., EPSP followed by AP) during induction of plasticity. Note that this new pairing order has no impact on plasticity. Inset shows long-term potentiation (tLTP) and timing dependent long-term depression (tLTD) in MSNs expressing dopamine D1 receptors recorded in B6.Cg-Tg (Drd1a-tdTomato) mice. (B,C) show respectively average tLTP and tLTD expressed as percent of control following stimulation of PFCx (circle), amygdala (square) and hippocampal (diamond) inputs.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4507144&req=5

Figure 3: (A) Each open symbol, representing an individual MSN, indicates changes of EPSP amplitudes expressed as percent of control and measured 20 min after induction. Symbols above and below broken line show tLTP and tLTD, respectively. Change of synaptic strength after induction is expressed as percent of control (100%). Open circles, squares and diamonds indicate EPSPs amplitude following stimulation of cortical, amygdala and hippocampal afferents, respectively. Red symbols with SEM show averaged overall changes. In parentheses are shown number of neurons recorded in each condition. Solid gray symbols indicate the magnitude of tLTD recorded in nine MSNs after reversing the pairing order (i.e., EPSP followed by AP) during induction of plasticity. Note that this new pairing order has no impact on plasticity. Inset shows long-term potentiation (tLTP) and timing dependent long-term depression (tLTD) in MSNs expressing dopamine D1 receptors recorded in B6.Cg-Tg (Drd1a-tdTomato) mice. (B,C) show respectively average tLTP and tLTD expressed as percent of control following stimulation of PFCx (circle), amygdala (square) and hippocampal (diamond) inputs.
Mentions: All experiments, with the exception of one where male B6.Cg-Tg (Drd1a-tdTomato) were used (inset, Figure 3A), were performed on male wild type (wt) and BK channel β4 knockout C57Bl/6J mice. All mice were handled according to the American Association for the Accreditation of Laboratory Animal Care guideline. The protocol was approved by the Institutional Animal Care and Use Committee of University of Massachusetts Medical School. Mice were maintained at constant temperature and humidity with a 12-h light–dark cycle. Water and food were provided ad libitum.

Bottom Line: It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol.However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive).Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School Worcester, MA, USA.

ABSTRACT
It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive). Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD) and long-term potentiation (LTP) and long-term potentiation (tLTP) and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

No MeSH data available.


Related in: MedlinePlus