Dataset Information

Adenosine A_2A Receptors in the Amygdala Control Synaptic Plasticity and Contextual Fear Memory.

ABSTRACT: The consumption of caffeine modulates working and reference memory through the antagonism of adenosine A_2A receptors (A_2ARs) controlling synaptic plasticity processes in hippocampal excitatory synapses. Fear memory essentially involves plastic changes in amygdala circuits. However, it is unknown if A_2ARs in the amygdala regulate synaptic plasticity and fear memory. We report that A_2ARs in the amygdala are enriched in synapses and located to glutamatergic synapses, where they selectively control synaptic plasticity rather than synaptic transmission at a major afferent pathway to the amygdala. Notably, the downregulation of A_2ARs selectively in the basolateral complex of the amygdala, using a lentivirus with a silencing shRNA (small hairpin RNA targeting A_2AR (shA_2AR)), impaired fear acquisition as well as Pavlovian fear retrieval. This is probably associated with the upregulation and gain of function of A_2ARs in the amygdala after fear acquisition. The importance of A_2ARs to control fear memory was further confirmed by the ability of SCH58261 (0.1 mg/kg; A_2AR antagonist), caffeine (5 mg/kg), but not DPCPX (0.5 mg/kg; A₁R antagonist), treatment for 7 days before fear conditioning onwards, to attenuate the retrieval of context fear after 24-48 h and after 7-8 days. These results demonstrate that amygdala A_2ARs control fear memory and the underlying process of synaptic plasticity in this brain region. This provides a neurophysiological basis for the association between A_2AR polymorphisms and phobia or panic attacks in humans and prompts a therapeutic interest in A_2ARs to manage fear-related pathologies.

SUBMITTER: Simoes AP

PROVIDER: S-EPMC5061896 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adenosine A2A Receptors in the Amygdala Control Synaptic Plasticity and Contextual Fear Memory.

Simões Ana Patrícia AP Machado Nuno J NJ Gonçalves Nélio N Kaster Manuella P MP Simões Ana T AT Nunes Ana A Pereira de Almeida Luís L Goosens Ki Ann KA Rial Daniel D Cunha Rodrigo A RA

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20160617 12

The consumption of caffeine modulates working and reference memory through the antagonism of adenosine A2A receptors (A2ARs) controlling synaptic plasticity processes in hippocampal excitatory synapses. Fear memory essentially involves plastic changes in amygdala circuits. However, it is unknown if A2ARs in the amygdala regulate synaptic plasticity and fear memory. We report that A2ARs in the amygdala are enriched in synapses and located to glutamaterg ...[more]

PMID: 27312408

Similar Datasets

Project description:BackgroundThe over-activation of adenosine A2A receptors (A2AR) is closely implicated in cognitive impairments of Alzheimer's disease (AD). Growing evidence shows that A2AR blockade possesses neuroprotective effects on AD. Spatial navigation impairment is an early manifestation of cognitive deficits in AD. However, whether A2AR blockade can prevent early impairments in spatial cognitive function and the underlying mechanism is still unclear.MethodsA transgenic APP/PS1 mouse model of AD amyloidosis was used in this study. Behavioral tests were conducted to observe the protective effects of A2AR blockade on early spatial memory deficits in 4-month old APP/PS1 mice. To investigate the underlying synaptic mechanism of the protective effects of A2AR blockade, we further examined long-term potentiation (LTP) and network excitation/inhibition balance of dentate gyrus (DG) region, which is relevant to unique synaptic functions of immature adult-born granule cells (abGCs). Subsequently, the protective effects of A2AR blockade on dendritic morphology and synaptic plasticity of 6-week-old abGCs was investigated using retrovirus infection and electrophysiological recordings. The molecular mechanisms underlying neuroprotective properties of A2AR blockade on the synaptic plasticity of abGCs were further explored using molecular biology methods.ResultsAPP/PS1 mice displayed DG-dependent spatial memory deficits at an early stage. Additionally, impaired LTP and an imbalance in network excitation/inhibition were observed in the DG region of APP/PS1 mice, indicating synaptic structural and functional abnormalities of abGCs. A2AR was found to be upregulated in the hippocampus of the APP/PS1 mouse model of AD. Treatment with the selective A2AR antagonist SCH58261 for three weeks significantly ameliorated spatial memory deficits in APP/PS1 mice and markedly restored LTP and network excitation/inhibition balance in the DG region. Moreover, SCH58261 treatment restored dendritic morphology complexity and enhanced synaptic plasticity of abGCs in APP/PS1 mice. Furthermore, SCH58261 treatment alleviated the impairment of synaptic plasticity in abGCs. It achieved this by remodeling the subunit composition of NMDA receptors and increasing the proportion of NR2B receptors in abGCs of APP/PS1 mice.ConclusionsBlockade of A2AR improves early spatial memory deficits in APP/PS1 mice, possibly by reversing synaptic defects of abGCs. This finding suggests that A2AR blockade could be a potential therapy for AD.

Dataset Information

Adenosine A_2A Receptors in the Amygdala Control Synaptic Plasticity and Contextual Fear Memory.

Publications

Adenosine A<sub>2A</sub> Receptors in the Amygdala Control Synaptic Plasticity and Contextual Fear Memory.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets