Much research on oestrogens has focused on their long-term action, exerting behavioural effects within hours to days through gene transcription. Oestrogens also affect behaviour on a much shorter time scale. These rapid effects are assumed to occur through cell signalling and can elicit a behavioural effect as early as 15 min after treatment. These effects on behaviour have primarily been explored through the action of oestradiol at three well-known oestrogen receptors (ERs): ERa, ERb and the more recently described G protein-coupled ER1 (GPER1). The rapid effects of oestradiol and ER agonists have been tested on both social and nonsocial learning paradigms. Social learning refers to a paradigm in which an animal acquires information and modifies its behaviour based on observation of another animal, commonly studied using the social transmission of food preferences paradigm. When administered shortly before testing, oestradiol rapidly improves social learning on this task, although no ER agonist has definitive, comparable improving effects. Some evidence points to GPER1, whereas ERa impairs, and ERb activation has no effect on social learning. Conversely, ERa and GPER1 play a larger role than ERb in the rapid improving effect of oestrogens on nonsocial learning, including social and object recognition. In addition, when administered immediately post-acquisition, oestrogens also rapidly improve memory consolidation in a variety of learning paradigms: object recognition, object placement, inhibitory avoidance and the Morris water maze, indicating that oestradiol affects the consolidation of multiple types of memory. Evidence suggests that these improvements are the result of oestrogens acting in the dorsal hippocampus where selective activation of all three ERs shows rapid improving effects on spatial learning comparable to oestradiol. However, the hippocampus is not necessary for rapid oestradiol improvements on social recognition. Although acute treatment with oestradiol enhances learning and memory on various social and nonsocial learning paradigms, the specific ERs play different roles in each type of learning. Future research should aim to further determine the roles of ERs with respect to the enhancing effects of oestradiol on learning and memory, and also determine where in the brain oestradiol acts to affect social and nonsocial learning.
Stereotypic behaviour (SB) occurs in certain human disorders (e.g. autism), and animals treated with stimulants or raised in impoverished conditions, including laboratory mice in standard cages. Dysfunctional cortico-basal ganglia pathways have been implicated in these examples, but for cage-induced forms of SB, the relative roles of ventral versus dorsal striatum had not been fully ascertained. Here, we used immunohistochemical staining of FosB and ΔFosB to assess long-term activation within the nucleus accumbens and caudate-putamen of C57BL/6 mice. Housed in typical laboratory cages, these mice spontaneously developed different degrees of route-tracing, bar-mouthing and other forms of SB (spending 0% to over 50% of their active time budgets in this behaviour). The most highly stereotypic mice showed the most elevated FosB/ΔFosB activity in the nucleus accumbens. No such patterns occurred in the caudate-putamen. The cage-induced SB common in standard-housed mice thus involves elevated activity within the ventral striatum, suggesting an aetiology closer to compulsive gambling, eating and drug-seeking than to classic amphetamine stereotypies and other behaviours induced by motor loop over-activation.
Acetylcholine (ACh) neurotransmission within the medial prefrontal cortex (mPFC) plays an important modulatory role to support mPFC-dependent cognitive functions. This role is mediated by ACh activation of its nicotinic (nAChR) and muscarinic (mAChR) classes of receptors, which are both present on mPFC layer VI pyramidal neurons. While the expression and function of nAChRs have been characterized thoroughly for rodent mPFC layer VI neurons during postnatal development, mAChRs have not been characterized in detail. We employed whole-cell electrophysiology with biocytin filling to demonstrate that mAChR function is greater during the juvenile period of development than in adulthood for both sexes. Pharmacological experiments suggest that each of the M1, M2, and M3 mAChR subtypes contributes to ACh responses in these neurons in a sex-dependent manner. Analysis of dendrite morphology identified effects of age more often in males, as the amount of dendrite matter was greatest during the juvenile period. Interestingly, a number of positive correlations were identified between the magnitude of ACh/mAChR responses and dendrite morphology in juvenile mice that were not present in adulthood. To our knowledge, this work describes the first detailed characterization of mAChR function and its correlation with neuron morphology within layer VI of the mPFC.
Stereotypic behaviours (SBs) are linked with behavioural inflexibility and resemble symptoms of autism, suggesting that stereotypic animals could have autistic-like social impairments. SBs are also common in caged mice. We therefore hypothesised relationships between stereotypic and social behaviours, predicting that highly stereotypic mice would give/receive more agonism and be less effective in social learning tasks. Experiment One used C57BL/6 and DBA/2 mice in non-enriched or enriched housing (15 cages each); Experiment Two, more cages (6 non-enriched, 44 enriched) plus a third strain (BALB/c). Across both experiments, enrichment reduced SB and agonism (aggression, plus 'displacements' where one mouse supplants another at a resource). These effects appeared related: housing effects on agonism became negligible when SB was statistically controlled for; and, at least in enriched cages, SB covaried with receiving aggression. In Experiment Three, 20 DBAs varying in SB from Experiment Two acted as demonstrators in a 'social transmission of food preferences' task. They were fed a novel flavour (shatavari powder), then each mingled with a familiar but flavour-naïve C57 observer. Observers were subsequently offered two novel flavours: shatavari or marjoram. Those spontaneously choosing more shatavari (n = 10) tended to have had less stereotypic demonstrators than the other 10 observer mice. Overall, highly stereotypic mice thus received more agonism-an effect with obvious welfare implications that can be reduced with enrichment-and seemed potentially less effective at inducing flavour preferences in conspecifics. Such effects are consistent with social impairment, suggesting that reducing SB may perhaps enhance interactions between conspecifics.
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