Abstract
The term “metaplasticity” is used to describe changes in synaptic plasticity sensitivity following an electrical, biochemical, or behavioral priming stimulus. For example, priming the basolateral amygdala (BLA) enhances long-term potentiation (LTP) in the dentate gyrus (DG) but decreases LTP in the CA1. However, the mechanisms underlying these metaplastic effects are only partly understood. Here, we examined whether the mechanism underlying these effects of BLA priming involves intra-BLA GABAergic neurotransmission. Low doses of muscimol, a GABAA receptor (GABAAR) agonist, were microinfused into the rat BLA before or after BLA priming. Our findings show that BLA GABAAR activation via muscimol mimicked the previously reported effects of electrical BLA priming on LTP in the perforant path and the ventral hippocampal commissure-CA1 pathways, decreasing CA1 LTP and increasing DG LTP. Furthermore, muscimol application before or after tetanic stimulation of the ventral hippocampal commissure-CA1 pathways attenuated the BLA priming-induced decrease in CA1 LTP. In contrast, muscimol application after tetanic stimulation of the perforant path attenuated the BLA priming-induced increase in DG LTP. The data indicate that GABAAR activation mediates metaplastic effects of the BLA on plasticity in the CA1 and the DG, but that the same GABAAR activation induces an intra-BLA form of metaplasticity, which alters the way BLA priming may modulate plasticity in other brain regions. These results emphasize the need for developing a dynamic model of BLA modulation of plasticity, a model that may better capture processes underlying memory alterations associated with emotional arousing or stressful events.
Highlights
The term “metaplasticity” [1] is used to describe changes in the ability to induce synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD) following a priming stimulus activating the synapses
To gain insight into GABAergic regulation of basolateral amygdala (BLA) modulation of synaptic plasticity in the dentate gyrus (DG) and the CA1, muscimol was microinfused into the BLA, either as a standalone manipulation or 10 min before or after priming of the BLA prior to LTP induction in the hippocampus [38,39]
We examined whether priming can be performed more than once to affect metaplasticity and whether this leads to accumulated priming effect, cancelation of the priming effect, or no change compared to the single priming, as well as how this compares to priming with muscimol
Summary
The term “metaplasticity” [1] is used to describe changes in the ability to induce synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD) following a priming stimulus activating the synapses. This lasting state change affecting future plasticity is often not apparent in synaptic efficacy following the initial bout of synaptic activity [2]. Studies have shown that both administration of stress hormones (e.g., corticosterone) and behavioral stress result in upregulation or downregulation of LTP, depending on the synapses and the timing of stimulus administration [5,6,7,8,9,10,11,12,13,14]. We and other groups have reported that BLA activation modulates hippocampal LTP, a synaptic model of memory [21,22,23,24,25]
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