Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral amygdala-dentate gyrus pathway of anesthetized rats.

We have previously found that the induction of long-term potentiation in the synaptic pathway from the basolateral amygdala to the dentate gyrus (BLA-DG LTP) is regulated by L-type Ca(2+) channels, dopamine D(2) receptors and GABAergic inhibition. In the present study, we investigated possible relations among the three mechanisms by using anesthetized rats. Blockade of GABAergic inhibition with picrotoxin abolished both the inhibitory effect of the dopamine D(2) receptor antagonist chlorpromazine and the promoting effect of the dopamine D(2) receptor agonist quinpirole on the induction of BLA-DG LTP. However, the inhibitory effect of the L-type Ca(2+) channel blocker verapamil on BLA-DG LTP was not affected by picrotoxin. These results suggest that the role of dopamine D(2) receptors in the induction of BLA-DG LTP is modulatory and depends on GABAergic inhibition, whereas the role of L-type Ca(2+) channels is fundamental.

Involvement of dopamine D2 receptors in the induction of long-term potentiation in the basolateral amygdala-dentate gyrus pathway of anesthetized rats.

We have previously found that synaptic pathway from the basolateral amygdala (BLA) to the dentate gyrus (DG) displays N-methyl-D-aspartate (NMDA) receptor-independent form of long-term potentiation (LTP), which should be a valuable model for elucidating neural mechanisms linking emotion and memory. To explore its cellular mechanisms, we investigated possible involvement of the beta-adrenergic, muscarinic cholinergic and dopaminergic systems on LTP in this pathway of anesthetized rats. The induction of BLA-DG LTP was not affected by administration of the beta-adrenoceptor antagonist propranolol (50-150nmol, i.c.v.), the muscarinic receptor antagonist scopolamine (2-6mg/kg, i.p.), the cholinesterase inhibitor physostigmine (50 nmol, i.c.v.) or the dopamine D(1) receptor antagonist SCH23390 (100nmol, i.c.v.), but significantly inhibited by the dopamine D2 receptor antagonists, chlorpromazine (15nmol, i.c.v.) and haloperidol (0.15-0.5mg/kg, i.p.), and significantly promoted by the dopamine D2 receptor agonist quinpirole (78nmol, i.c.v.). Furthermore, lesioning with 6-hydroxydopamine of the ventral tegmental area (VTA), the origin of mesolimbic dopaminergic neurons, resulted in attenuated BLA-DG LTP. These results suggest that the D2-dopaminergic system, but not the beta-adrenergic, muscarinic or D1-dopaminergic system, is involved in the induction of BLA-DG LTP. In addition, inhibition of BLA-DG LTP by haloperidol or VTA lesion was abolished by blockade of GABAergic inhibition with picrotoxin. It is probable that the D2-dopaminergic system promotes the induction of BLA-DG LTP by suppressing GABAergic inhibition.

Involvement of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral amygdala-dentate gyrus pathway of anesthetized rats.

We have recently found that synaptic pathway from the basolateral amygdala (BLA) to the dentate gyrus (DG) displays N-methyl-D-aspartate (NMDA) receptor-independent form of long-term potentiation (LTP), which should be a valuable model for elucidating neural mechanisms linking emotion and memory. To explore its cellular mechanisms, we investigated the effects of L-type Ca(2+) channel blockers on LTP in this pathway of anesthetized rats. Intraperitoneal administration of verapamil (3-30 mg/kg) or diltiazem (6-20 mg/kg) significantly impaired the induction of LTP following high-frequency stimulation. When verapamil was administered after high-frequency stimulation, it did not affect the pre-established LTP. These results suggest that activation of L-type Ca(2+) channels is necessary for the induction of LTP in the BLA-DG pathway.

The induction of long-term potentiation at amygdalo-hippocampal synapses in vivo.

Electrical stimulation of the basolateral amygdala (BLA) evoked synaptic potentials in the dentate gyrus (DG) of the hippocampus in anesthetized rats. To determine if this pathway possesses synaptic plasticity, we investigated the impact of several conditions of high-frequency stimulation on BLA-DG synaptic potentials in these rats. Application of two trains of 100-pulse, 100-Hz stimulation or theta-burst stimulation to the BLA reproducibly induced long-term potentiation (LTP) of BLA-DG synaptic potentials. Paired-pulse facilitation was unchanged during LTP, suggesting that postsynaptic mechanisms are involved in the expression of LTP. In addition, the induction of LTP was not affected by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate, suggesting that activation of NMDA receptors is not required. This novel form of LTP should be a valuable model for elucidating neural mechanisms underlying the formation of emotional memory.