94 research outputs found
Antagonizing Dorsal Hippocampal Dopamine D1-type Receptors Affects Social Learning and Social Interactions but not Food Intake in Male and Female Mice
No full textDopamine (DA) is involved in many motivationally relevant behaviors, including social learning, feeding, and social interactions. With systemic treatments, our lab has previously found an involvement of DA D1-type receptors in the social transmission of food preferences (STFP; Choleris et al., 2011), however, the site(s) of action remain unknown. The ventral tegmental area has dopaminergic projections to the hippocampus—a site important for social learning in the STFP. In this study, we microinfused the DA D1-type receptor antagonist SCH23390 into the dorsal hippocampus of adult male and female mice. We found that SCH23390 blocked social learning in both male and female mice without influencing total food intake. While there was a sex-specific effect of SCH23390 on certain social behaviors, there was no significant influence of drug treatment on oronasal investigation, or olfactory discrimination, for either sex. Thus, hippocampal DA D1-type receptors may play an important role in the ‘social brain’.Natural Sciences and Engineering Research Council of Canad
Mesolimbic Dopamine, Its Receptors and Social Learning
No full textThis thesis investigated the role of dopamine (DA) in the social transmission of food preferences (STFP) in male and female mice. A study conducted by Choleris et al., 2011 using systemic treatments found a role for DA D1-type receptors (D1, D5) in social learning, and a role for DA D2-type receptors (D2, D3, D4) in feeding behavior in the STFP in mice. The potential brain region(s) of action underlying these effects are only now being investigated. The ventral tegmental area (VTA) has dopaminergic projections to limbic structures including the hippocampus and nucleus accumbens (NAc). Previous work done in our lab finds that infusing the DA D1-type receptor antagonist SCH23390 into the dorsal hippocampus blocks social learning in male and female mice (Matta et al., 2017). This thesis found that infusing the DA D2-type receptor antagonist Raclopride into the dorsal hippocampus blocks social learning in female, but not male mice. This social learning impairment due to intrahippocampal Raclopride could not be explained by changes in total food intakes, exposure to the socially carried diet odor, or changes in olfactory discrimination between the two foods used during the choice test. Blocking hippocampal DA D2-type receptors also sex-dependently mediated the social interactions, whereby males had a greater reduction in agonistic-type behaviors, while females had a greater reduction in social investigatory-type behaviors. Using in vivo microdialysis, we further found that social learning in the STFP was associated with increased hippocampal DA release for males, whereas social learning was associated with decreased hippocampal DA release for females. This sex difference in hippocampal DA release during the STFP could not be explained by differences in the exposures to the socially carried food odor. Lastly, infusing SCH23390 into the shell of the NAc did not affect social learning or feeding behavior in the STFP in either male nor female mice. However, there were effects of intra-NAc SCH23390 on the social interactions, including reductions in social behaviors such as social investigation and agonistic behaviors for both sexes. Thus, mesolimbic DA and its receptors sex-dependently mediate the STFP in mice.Natural Sciences and Engineering Research Council of Canad
Expanding the Link between Out-Group Threats and In-Group Behavior:(A Reply to Kavaliers and Choleris)
No full textIn social species, groups and their members face a variety of threats from conspecific outsiders. Such out-group conflict is predicted to influence within-group behavior, with empirical work demonstrating this link in humans, primates, and birds. In our note “Out-Group Threat Promotes Within-Group Affiliation in a Cooperative Fish,” appearing in The American Naturalist in February 2016, we provided experimental evidence that simulated territorial intrusions result in subsequent increases in affiliation among groupmates in a cichlid fish (Neolamprologus pulcher). Martin Kavaliers and Elena Choleris, in their comment “Out-Group Threat Responses, In-Group Bias, and Nonapeptide Involvement Are Conserved Across Vertebrates,” appearing in this issue, commented on our cichlid-fish article; they consider the conserved nature of the link between out-group threat and in-group behavior and bias in vertebrates, the influence of pathogens in the process, and the potential underpinning hormonal mechanisms. Here, we provide clarification and expansion of some of the core points that are discussed in the comment by Kavaliers and Choleris
The role of specific estrogen receptors in mediating rapid estrogenic improvements of social learning in female mice
No full textSocial learning is a process by which an animal gains information from another; however much of the research on estrogens effects on learning focuses on individual learning tasks. We therefore examined the effects of 17-estradiol (17beta-E2) and agonists for the estrogen receptors (ERs) ER-alpha, ER-beta, and the G protein-coupled ER 1 (GPER1) on the social transmission of food preferences (STFP) task, within a time scale allowing us to determine the rapid effects of estrogens. General ER activation with 17beta-E2 rapidly improved social learning on this task. Specific activation of the GPER1 also rapidly improved social learning, suggesting that 17beta-E2 acts through the GPER1 to rapidly improve learning on the STFP. Activation of ER-alpha and ER-beta activation, however, induced some impairing effects on learning. Rapid estrogenic modulation of social learning in the STFP therefore likely depends on the receptors activated, as each ER differently affected learning on this task
The Role of Membrane-Bound Receptors in the Rapid Estrogenic Enhancements of Learning and Memory Within the Hippocampus
No full textEstrogens play a role in learning and memory on a rapid time scale. Systemic treatment with 17β-estradiol rapidly improves object recognition, social recognition and object place learning in ovariectomized female mice within a timescale of only 40 minutes following administration. Studies have identified the dorsal hippocampus as one site of these estrogenic enhancing effects. Whether these rapid estrogenic effects are mediated solely by membrane-bound estrogen receptors is currently unknown. This study sought to determine the role of membrane estrogen receptors in the rapid effects of 17-β estradiol within the hippocampus. By conjugating 17-β estradiol to a large bovine serum albumin molecule (BSA-E2), the estradiol is prevented from passing through the cellular membrane and thus, from binding to intracellular receptors. We were able to demonstrate that the rapid effects of estrogens on learning and memory are mediated by membrane-bound estrogen receptors, independent of intracellular mechanisms
Rapid Estrogenic Effects in the Medial Prefrontal Cortex on Short-Term Social and Non-Social Memory in Male Mice
No full textSex steroids can rapidly modulate neuronal structure and behaviour. The estrogen 17-estradiol (E2) modulates numerous cognitive processes in both sexes showing varying molecular and behavioural effects when administered in different brain regions. When administered into the medial prefrontal cortex (mPFC) of ovariectomized female mice, E2 rapidly facilitated two social but not two non-social cognitive processes. The suggested preferential facilitation of social instead of non-social cognition in females has not been tested in males. Therefore, the present study investigated the rapid effects of E2 in the mPFC of male mice during one social and two non-social short-term memory (STM) tasks: social recognition, object recognition and object placement. The rapid effects of E2 during a STM task was also examined through quantifying rapid changes in dendritic spine density. Results demonstrated that E2 rapidly facilitated social and non-social STM in the mPFC and suggests increases in dendritic spine density as a potential mechanism
Rapid Effects of Estrogens and Androgens on Social and Non-Social Short-Term Memory in the Dorsal Hippocampus of Male Mice
No full textIt has been established that sex-steroid hormones can rapidly influence memory independently of gene transcription. Previous studies have shown that estradiol (E2) facilitates social and non-social short-term memory (STM) in the dorsal hippocampus (dHPC) of ovariectomized female mice. However, the rapid effects of estrogens and androgens on STM in the dHPC of male mice have yet to be elucidated. Therefore, this thesis investigated the rapid effects of E2 and dihydrotestosterone (DHT) on three STM paradigms: object placement, object recognition, and social recognition, in the dHPC of castrated (CX) male mice. Rapid effects of E2 and DHT on neuronal plasticity were also examined through hippocampal dendritic spine density changes. Results suggest E2 and DHT rapidly facilitate social and non-social STM in the dHPC of males and increase CA1 hippocampal dendritic spine density. This demonstrates both E2 and DHT rapidly affects male cognition and dHPC neuronal plasticity
Effects of an Oxytocin Receptor Antagonist on Estrogens’ Facilitative Effects on Social Recognition in the Medial Amygdala on Female Mice
No full textEstrogens and oxytocin have shown to facilitate social recognition. Estrogens have been implicated in mediating oxytocin and oxytocin receptor production. Estrogens can rapidly facilitate social recognition in the paraventricular nucleus and medial amygdala, and an oxytocin receptor antagonist (OTRA) has prevented social recognition. We predicted estrogens’ rapid mediation of oxytocin would facilitate social recognition, occurring in the medial amygdala itself. We examined whether 17-estradiol (E2) in the medial amygdala could rapidly facilitate social recognition. Next, we investigated if this process was mediated by oxytocin binding to its receptors. Lastly, we confirmed E2 rapid facilitation of recognition in the medial amygdala is social specific. We found E2 in the medial amygdala rapidly facilitates social recognition; E2’s effect on social recognition is blocked by OTRA; and E2 did not rapidly facilitate object recognition. This suggests estrogens’ rapid effects on social recognition in the medial amygdala occurs through a modulation of oxytocin.Natural Sciences and Engineering Research Council of Canad
Mechanisms Underlying the Rapid Facilitation of Short-Term Social Recognition Memory by Estrogens in Female Mice
No full textThis dissertation explores some of the mechanisms underlying the rapid facilitating effects of estrogens on short-term social recognition memory in female mice. It has recently been shown that estrogens and estrogen receptor agonists can rapidly facilitate short-term social recognition memory within 40 minutes of systemic or intra-hippocampal administration. However, the mechanisms driving this facilitation are not yet known. Therefore, we explored whether 1) the extracellular signal-regulated kinase (ERK) or phosphoinositide 3-kinase (PI3K) cell signalling pathways and/or 2) actin polymerization or protein synthesis in the dorsal hippocampus are necessary to the rapid facilitating effects of estrogens or short-term social recognition memory in ovariectomized female mice. Furthermore, in order to explore the involvement of estrogens in other regions in the “social brain”, we investigated whether 3) estrogens or estrogen receptor agonists in the medial nucleus of the amygdala (MeA) could rapidly facilitate short-term social recognition memory. We found that 1) inhibition of either the ERK or PI3K pathway blocks estrogen-facilitated short-term social recognition memory. Estrogen receptor (ER) alpha requires both the ERK and PI3K pathways, whereas the G protein-coupled estrogen receptor 1 (GPER1) requires only the PI3K pathway, to facilitate short-term social recognition memory. Both 2) actin polymerization and protein synthesis, but not gene transcription, are required for rapid estrogen-facilitated short-term social recognition memory. Finally, 3) estrogens in the MeA can facilitate short-term social recognition memory and this appears to be driven by ERalpha, ERbeta, and the GPER1. Together, these data suggest that complex and concurrent intracellular processes drive the rapid effects of estrogens on short-term social recognition memory in the dorsal hippocampus and that regions other than the dorsal hippocampus play a role in the rapid effects of estrogens on social cognition.Natural Sciences and Engineering Research Council of Canad
Mechanisms of Social Learning in Female Mice: The Roles of Estrogens and Muscarinic Acetylcholine Signaling
No full textSocial learning is a common, adaptive learning strategy in animals and humans, in which an individual acquires information or skills from another in their social group. Despite its importance to human and animal learning, social learning has received relatively little research attention, and we thus are only beginning to understand the neurobiological mechanisms underlying this type of cognition. In this thesis, I investigated the roles of the rapid effects of estrogens and the effects of acetylcholine signaling at muscarinic receptors in short- and long-term memory for socially learned information using the Social Transmission of Food Preferences (STFP) task in mice, in which an observer mouse preferentially consumes a novel food that they had previously smelled on the breath of a conspecific demonstrator mouse. Estradiol rapidly (within 45 minutes) and activation of the G protein-coupled estrogen receptor 1 (GPER1) with the agonist G1 facilitate short-term STFP memory on the STFP when administered systemically. The first part of this thesis focuses on the brain regions in which estrogens may act to facilitate social learning. We therefore infused estradiol into the dorsal hippocampus and basolateral amygdala of female ovariectomized (OVX) mice. Second, we investigated muscarinic acetylcholine signaling as a possible downstream mechanism of estradiol and G1’s rapid facilitatory effects. We tested this by co-administering doses of estradiol or G1 previously found to facilitate STFP memory with a subeffective dose of the muscarinic receptor antagonist scopolamine before testing short-term STFP memory. Finally, we sought to determine which muscarinic receptor subtypes mediate the impairing effects of scopolamine on the STFP. We first tested the effects of scopolamine on long-term STFP memory in ovariectomized and gonadally intact female mice. We then tested the effects of the M1 antagonist dicyclomine and the M2 antagonist AF-DX 116 on long-term STFP memory. Through these investigations, we found that while estradiol did not facilitate short-term STFP memory when infused into the hippocampus or basolateral amygdala, it may facilitate short-term memory by enhancing acetylcholine at muscarinic receptors. Lastly, we found that muscarinic receptor signaling is also necessary for long-term STFP memory in gonadally intact female mice and that the M1 receptor subtype is one of the muscarinic receptors mediating this effect
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