GABAergic Transmission in the Basolateral Amygdala Differentially Modulates Plasticity in the Dentate Gyrus and the CA1 Areas

Int J Mol Sci. 2020 May 27;21(11):3786. doi: 10.3390/ijms21113786.

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.

Keywords: CA1; GABA; basolateral amygdala; dentate gyrus; metaplasticity; synaptic plasticity.

MeSH terms

  • Animals
  • Basolateral Nuclear Complex / drug effects
  • Basolateral Nuclear Complex / physiology*
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology*
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology*
  • Electrodes
  • Long-Term Potentiation / drug effects
  • Male
  • Muscimol / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Perforant Pathway / drug effects
  • Perforant Pathway / physiology
  • Rats, Sprague-Dawley
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Muscimol
  • gamma-Aminobutyric Acid