AMPA receptors in the medial amygdala are critical for establishing a neuroendocrine memory in the female rat

Abstract

We sought to examine AMPA receptor (AMPAR) function in the medial posterodorsal amygdala (MePD), as glutamate neurotransmission is critical for the neural response to vaginal-cervical stimulation that initiates pregnancy or pseudopregnancy. Female rats were infused with the AMPAR antagonist CNQX or vehicle directly into the MePD via bilaterally implanted cannulae, then either returned to their homecage (HC), or received 15 mounts-without-intromissions (MO) or 15 intromissions (15I) from a male. Expression of the activity marker EGR-1 was used to determine the CNQX concentration which would prevent mating-induced activation of MePD neurons. Separate cannulated females received CNQX infusions into the MePD prior to receiving 15I, and the oestrous cycle length was monitored by daily vaginal lavages. Infusion of CNQX (500 nm) blocked mating-induced neural activation and lengthened the oestrous cycle, demonstrating AMPAR involvement in the formation of pseudopregnancy. To further explore this involvement, separate groups of 15I, MO and HC females were killed 90 min or 3 h after testing treatment. Brain sections were immunolabeled for AMPAR-subunit GluR1 phosphorylated at one of two sites (Serine-831 or Serine-845), or total GluR1 and GluR2, and immunofluorescence intensity was measured in the MePD, hippocampus and hypothalamus. A mating-induced increase in Serine-831 phosphorylation after 3 h was observed only in the MePD, whereas there was no effect on Serine-845 phosphorylation. Additionally, we observed a time-dependent increase in total GluR1 staining intensity. These results suggest an increased AMPAR function in the MePD after receipt of VCS, and a role for AMPAR in the neural response to VCS resulting in pseudopregnancy.

GnRH pulse generator frequency is modulated by kisspeptin and GABA‐glutamate interactions in the posterodorsal medial amygdala in female mice

“…Therefore, these two neurotransmitters are sensible candidates to be used by the amygdala neuronal networks underlying the upstream, extra‐hypothalamic regulation of the GnRH pulse generator. Unsurprisingly, both GABA and glutamate neurons are found in the MePD, 4,5 and pharmacological antagonism of both has deleterious effects on several aspects of reproductive physiology 6–8 . In rats, blocking AMPA and NMDA glutamate receptors with CNQX and AP5, respectively, impedes activation of MePD neurons in response to vaginal‐cervical stimulation, thereby preventing the pregnancy or pseudopregnancy response following intromission; AMPA antagonism also disrupts oestrous cycles 6,7 .…”

“…Unsurprisingly, both GABA and glutamate neurons are found in the MePD, 4,5 and pharmacological antagonism of both has deleterious effects on several aspects of reproductive physiology. [6][7][8] In rats, blocking AMPA and NMDA glutamate receptors with CNQX and AP5, respectively, impedes activation of MePD neurons in response to vaginal-cervical stimulation, thereby preventing the pregnancy or pseudopregnancy response following intromission; AMPA antagonism also disrupts oestrous cycles. 6,7 Furthermore, MePD NMDA and GABA A receptor (GABA A R) antagonism causes a weight-independent advancement of puberty.…”

Repeated administration of estradiol promotes mechanisms of sexual excitation and inhibition: Glutamate signaling in the ventromedial hypothalamus attenuates excitation

“…GABAergic projections to the vlVMH arise largely from the mPOA, a region that is critical in the display of sexually appetitive behaviors, but a smaller projection also arises from the MeA [17]. The posterodorsal MeA (pdMeA) is implicated in the neuroendocrine changes necessary for the maintenance of pregnancy (or pseudopregnancy) following VCS, via activation of the ionotropic glutamatergic receptors AMPA [35] and NMDA [28,44]. The MeA contains a large number of estrogen receptors [37], and crystalline estradiol applied to this region facilitates lordosis as it does in the VMH [29].…”

GnRH pulse generator frequency is modulated by kisspeptin and GABA-glutamate interactions in the posterodorsal medial amygdala in female mice

“…Unsurprisingly, both GABA and glutamate neurons are found in the MePD (Choi et al, 2005;Westberry and Meredith, 2016), and pharmacological antagonism of both has deleterious effects on several aspects of reproductive physiology (Oberlander et al, 2009;Polston et al, 2001, Li et al, 2015. In rats, blocking AMPA and NMDA glutamate receptors with CNQX and AP5, respectively, impedes activation of MePD neurons in response to vaginal-cervical stimulation, thereby preventing the pregnancy or pseudopregnancy response following intromission; AMPA antagonism also disrupts estrous cycles (Oberlander et al, 2009;Polston et al, 2001). Furthermore, MePD NMDA and GABA A R antagonism causes a weight-independent advancement of puberty (Li et al, 2015).…”

“…Therefore, these two neurotransmitters are sensible candidates to be used by the amygdala neuronal networks underlying the upstream, extra-hypothalamic regulation of the GnRH pulse generator. Unsurprisingly, both GABA and glutamate neurons are found in the MePD (Choi et al ., 2005; Westberry and Meredith, 2016), and pharmacological antagonism of both has deleterious effects on several aspects of reproductive physiology (Oberlander et al ., 2009; Polston et al ., 2001, Li et al ., 2015). In rats, blocking AMPA and NMDA glutamate receptors with CNQX and AP5, respectively, impedes activation of MePD neurons in response to vaginal-cervical stimulation, thereby preventing the pregnancy or pseudopregnancy response following intromission; AMPA antagonism also disrupts estrous cycles (Oberlander et al ., 2009; Polston et al ., 2001).…”