Sexually Dimorphic Synaptic Organization of the Medial Amygdala

Abstract

The medial amygdala is important in social behaviors, many of which differ between males and females. The posterodorsal subnucleus of the medial amygdala (MeApd) is particularly sensitive to gonadal steroid hormones and is a likely site for gonadal hormone regulation of sexually dimorphic social behavior. Here we show that the synaptic organization of the MeApd in the rat is sexually dimorphic and lateralized before puberty. With the use of whole-cell voltage-clamp recording and quantitative electron microscopy, we found that, specifically in the left hemisphere, prepubertal males have ϳ80% more excitatory synapses per MeApd neuron than females. In the left but not the right MeApd, miniature EPSC (mEPSC) frequency was significantly greater in males than in females; mEPSC amplitude was not sexually dimorphic. Paired-pulse facilitation of EPSCs, an index of release probability, also was not sexually dimorphic, suggesting that greater mEPSC frequency is caused by a difference in excitatory synapse number. Electron microscopy confirmed that the asymmetric synapse-to-neuron ratio and the total asymmetric synapse number were significantly greater in the left MeApd of males than of females. In contrast to results for excitatory synapses, we found no evidence of sexual dimorphism or laterality in inhibitory synapses. Neither the frequency nor the amplitude of mIPSCs was sexually dimorphic or lateralized. Likewise, the number of symmetric synapses measured with electron microscopy was not sexually dimorphic. These findings show that the excitatory synaptic organization of the left MeApd is sexually differentiated before puberty, which could provide a sexually dimorphic neural substrate for the effects of hormones on adult social behavior.

Sex Differences in the Cannabinoid Modulation of Appetite, Body Temperature and Neurotransmission at POMC Synapses

“…Presently we show that females exhibit a higher degree of tonic glutamatergic synaptic input onto POMC neurons than do males, and that WIN 55,212-2 presynaptically inhibits glutamate release with equivalent potency and efficacy in females and males. This increased basal level of glutamatergic neurotransmission in females is consistent with sex differences in N-methyl- D -aspartate receptor-mediated regulation of A 12 dopamine neurons [46], and may reflect either an increased number of asymmetric synapses impinging on POMC neurons as has been described for sex differences in the synaptic organization of the medial amygdala [47], or a comparatively larger number of vesicular glutamate versus GABA transporters like those expressed in dual-phenotype amino acid neurotransmitter-containing nerve terminals impinging on GnRH neurons [48]. On the other hand, the agonist presynaptically inhibits GABAergic neurotransmission at POMC synapses with an approximately sixfold greater potency in females than in males.…”

Dose and Time Effects of Estrogen on Expression of Neuron-Specific Protein and Cyclic AMP Response Element-Binding Protein and Brain Region Volume in the Medial Amygdala of Ovariectomized Rats

“…Volume differences among estrogen regimens in the present study may be due to an estrogen effect on cell survival and/or an effect of ovariectomy on apoptosis or another form of degeneration. That estrogen maintains cell soma size [42], and enhances growth of dendritic [89] and synaptic structures in the MeA [51, 89, 90] is well-documented, and there is extensive evidence for a role of estrogen in neuroprotection. These alterations may be due to a region-specific effect of E2 on BDNF in the MeA (but not CeA) [2].…”

Emotional Memory in Early Steroid Abnormalities: An fMRI Study of Adolescents With Congenital Adrenal Hyperplasia

“…Pre-natal and early life androgen levels were also shown to influence sex differences in amygdala shape and synaptic function in juvenile rats (Cooke, Hegstrom, Villeneuve, & Breedlove, 1998;Cooke & Woolley, 2005;Wilson & Davies, 2007). Behaviorally, pre-natal and early life androgen levels were reported to reduce social memory function (Hebbard et al, 2003), and to sexually differentiate visual discrimination learning and spatial memory performance in mammal offspring (Hagger & Bachevalier, 1991;Roof, 1993).…”