Abstract
Adenosine A2A receptors (A2AR) are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR are involved in the control of prefrontal cortex (PFC)-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A2AR control glutamatergic synapse plasticity within the medial PFC (mPFC). To elucidate that, we tested whether A2AR blockade affects long-term plasticity (LTP) of excitatory post-synaptic potentials in pyramidal neurons and fast spiking (FS) interneurons in layer 5 of the mPFC and of population spikes. Our results show that A2AR are enriched at mPFC synapses, where their blockade reversed the direction of plasticity at excitatory synapses onto layer 5 FS interneurons from LTP to long-term depression, while their blockade had no effect on the induction of LTP at excitatory synapses onto layer 5 pyramidal neurons. At the network level, extracellularly induced LTP of population spikes was reduced by A2AR blockade. The interneuron-specificity of A2AR in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.
| Original language | English |
|---|---|
| Article number | 133 |
| Pages (from-to) | 1-12 |
| Number of pages | 12 |
| Journal | Frontiers in Pharmacology |
| Volume | 9 |
| Issue number | 20 March |
| DOIs | |
| Publication status | Published - 20 Mar 2018 |
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Keywords
- A receptor
- Adenosine
- Electrophysiology
- Fast-spiking interneurons
- LTP and LTD
- Prefrontal cortex (PFC)
- Synaptic plasticity
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Adenosine A2A receptors control glutamatergic synaptic plasticity in fast spiking interneurons of the prefrontal cortex. / Kerkhofs, Amber; Canas, Paula M.; Timmerman, A. J.; Heistek, Tim S.; Real, Joana I.; Xavier, Carolina; Cunha, Rodrigo A.; Mansvelder, Huibert D.; Ferreira, Samira G.
In: Frontiers in Pharmacology, Vol. 9, No. 20 March, 133, 20.03.2018, p. 1-12.Research output: Contribution to Journal › Article › Academic › peer-review
TY - JOUR
T1 - Adenosine A2A receptors control glutamatergic synaptic plasticity in fast spiking interneurons of the prefrontal cortex
AU - Kerkhofs, Amber
AU - Canas, Paula M.
AU - Timmerman, A. J.
AU - Heistek, Tim S.
AU - Real, Joana I.
AU - Xavier, Carolina
AU - Cunha, Rodrigo A.
AU - Mansvelder, Huibert D.
AU - Ferreira, Samira G.
PY - 2018/3/20
Y1 - 2018/3/20
N2 - Adenosine A2A receptors (A2AR) are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR are involved in the control of prefrontal cortex (PFC)-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A2AR control glutamatergic synapse plasticity within the medial PFC (mPFC). To elucidate that, we tested whether A2AR blockade affects long-term plasticity (LTP) of excitatory post-synaptic potentials in pyramidal neurons and fast spiking (FS) interneurons in layer 5 of the mPFC and of population spikes. Our results show that A2AR are enriched at mPFC synapses, where their blockade reversed the direction of plasticity at excitatory synapses onto layer 5 FS interneurons from LTP to long-term depression, while their blockade had no effect on the induction of LTP at excitatory synapses onto layer 5 pyramidal neurons. At the network level, extracellularly induced LTP of population spikes was reduced by A2AR blockade. The interneuron-specificity of A2AR in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.
AB - Adenosine A2A receptors (A2AR) are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR are involved in the control of prefrontal cortex (PFC)-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A2AR control glutamatergic synapse plasticity within the medial PFC (mPFC). To elucidate that, we tested whether A2AR blockade affects long-term plasticity (LTP) of excitatory post-synaptic potentials in pyramidal neurons and fast spiking (FS) interneurons in layer 5 of the mPFC and of population spikes. Our results show that A2AR are enriched at mPFC synapses, where their blockade reversed the direction of plasticity at excitatory synapses onto layer 5 FS interneurons from LTP to long-term depression, while their blockade had no effect on the induction of LTP at excitatory synapses onto layer 5 pyramidal neurons. At the network level, extracellularly induced LTP of population spikes was reduced by A2AR blockade. The interneuron-specificity of A2AR in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.
KW - A receptor
KW - Adenosine
KW - Electrophysiology
KW - Fast-spiking interneurons
KW - LTP and LTD
KW - Prefrontal cortex (PFC)
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=85044114631&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044114631&partnerID=8YFLogxK
U2 - 10.3389/fphar.2018.00133
DO - 10.3389/fphar.2018.00133
M3 - Article
VL - 9
SP - 1
EP - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
IS - 20 March
M1 - 133
ER -