Lucas Fürstenau de Oliveira

Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval

During the last decade, a considerable amount of evidence has accumulated to show that oxytocin (OT) is involved with functions other than its classical roles in reproduction-associated processes, such as social recognition, maternal behavior and neuroendocrine regulation of the stress response. It has been shown, for instance, that post-training systemic administration of oxytocin in mice produces an amnestic effect on the step-through inhibitory avoidance. Since it is still unclear how systemic levels of OT may affect CNS memory processes, our aim here was to investigate the hypothesis that systemic OT effects on memory retrieval might be mediated through an oxytocin-induced decrease in glucocorticoid release. In our first experiment, we have found an amnestic effect of i.p. pre-test 0.4 microg/kg of OT upon memory retrieval in the inhibitory avoidance task (IA); this OT dose was shown to (a) significantly decrease plasma corticosterone levels when compared to the saline group, and (b) not to cause any anxiety effects by itself in a plus-maze task. At last, an ineffective-by-itself dose of dexamethasone was able to reverse the amnestic effect of this OT dose. Our results suggest that the amnestic effect of systemically administered oxytocin upon memory retrieval in the inhibitory avoidance task was probably caused by an oxytocin-induced decrease in glucocorticoid release from the adrenal gland.

Glial alterations in the hippocampus of rats submitted to ibotenic-induced lesion of the nucleus basalis magnocellularis

Lesion of the nucleus basalis magnocellularis (nbm) is a suitable approach to study cognitive deficit and behavior alterations involving cholinergic dysfunction, which is associated with the major types of dementia. Cortical astrogliosis also has been described in this model, but it is not clear whether hippocampal astrocytes are activated. In this study, we investigated possible specific astrocyte alterations in the hippocampi of Wistar rats submitted to nbm damage with ibotenic acid, investigating the content and immunohistochemistry of glial fibrillary acidic protein (GFAP), as well as S100B protein content, glutamate uptake and glutamine synthetase activity on the 7th and 28th post-lesion days. Cognitive deficit was confirmed by the step-down inhibitory avoidance task. Interestingly, we found a decrease in GFAP content, S100B content and glutamate uptake activity in the hippocampus on the 28th day after nbm lesion. No alterations were observed in glutamine synthetase activity or in the cerebrospinal fluid S100B content. Although our data suggest caution in the use of nbm lesion with ibotenic acid as a dementia model, it is possible that these alterations could contribute to the cognitive deficit observed in these rats.

Facilitatory effect of the intra-hippocampal pre-test administration of MT3 in the inhibitory avoidance task

The cholinergic system plays a crucial role in learning and memory. Modulatory mechanisms of this system in the acquisition and consolidation processes have been extensively studied, but their participation in the memory retrieval process is still poorly understood. Conventional pharmacological agents are not highly selective for particular muscarinic acetylcholine receptor subtypes. Muscarinic toxins (MTs) that are highly selective for muscarinic receptors were extracted from the venom of the mamba snake, like the toxin MT3, selective for the M4 receptor subtype. These toxins are useful tools in studies of the specific functions of the M4 mediated transmission. The M4 receptor selective antagonist MT3, given into the dorsal hippocampus before the test, have enhanced the memory retrieval of an inhibitory avoidance task in rats. MT3 had no effect in the habituation to a new environment, including basic motor parameters, meaning that the effect in he inhibitory avoidance is purely cognitive. Our results suggest an endogenous negative modulation of the cholinergic muscarinic system upon the retrieval of previously consolidated aversive memories, hereby shown by the facilitatory effect of MT3.

Novel learning accelerates systems consolidation of a contextual fear memory

After initial encoding memories may undergo a time‐dependent reorganization, becoming progressively independent from the hippocampus (HPC) and dependent on cortical regions such as the anterior cingulate cortex (ACC). Although the mechanisms underlying systems consolidation are somewhat known, the factors determining its temporal dynamics are still poorly understood. Here, we studied the influence of novel learning occurring between training and test sessions on the time‐course of HPC‐ and ACC‐dependency of contextual fear conditioning (CFC) memory expression. We found that muscimol was disruptive when infused into the HPC up to 35 days after training, while the ACC is vulnerable only after 45 days. However, when animals were subjected to a series of additional, distinct tasks to be learned within the first 3 weeks, muscimol became effective sooner. Muscimol had no effect in the HPC at 20 days after training, exactly when the ACC becomes responsive to this treatment. Thus, our data indicates that the encoding of new information generates a tight interplay between distinct memories, accelerating the reorganization of previously stored long term memories between the hippocampal and cortical areas.