Search

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation. [ABSTRACT FROM AUTHOR]

Deficits in hippocampus‐dependent memory processes are common across psychiatric and neurodegenerative disorders such as depression, anxiety and Alzheimer's disease. Moreover, stress is a major environmental risk factor for these pathologies and it exerts detrimental effects on hippocampal functioning via the activation of hypothalamic–pituitary–adrenal (HPA) axis. The medial septum cholinergic neurons extensively innervate the hippocampus. Although, the cholinergic septohippocampal pathway (SHP) has long been implicated in learning and memory, its involvement in mediating the adaptive and maladaptive impact of stress on mnemonic processes remains less clear. Here, we discuss current research highlighting the contributions of cholinergic SHP in modulating memory encoding, consolidation and retrieval. Then, we present evidence supporting the view that neurobiological interactions between HPA axis stress response and cholinergic signalling impact hippocampal computations. Finally, we critically discuss potential challenges and opportunities to target cholinergic SHP as a therapeutic strategy to improve cognitive impairments in stress‐related disorders. We argue that such efforts should consider recent conceptualisations on the dynamic nature of cholinergic signalling in modulating distinct subcomponents of memory and its interactions with cellular substrates that regulate the adaptive stress response. [ABSTRACT FROM AUTHOR]