Inhibition of the LH Surge by Restraint Stress in Cyclic Rats: Studies on the Role of GABAA and GABAB Receptors

There is evidence that stress can alter the activity in the brain of gamma-aminobutyricacid (GABA), a neurotransmitter that has been implicated in the regulation of LH secretion. In the present study the role of GABA in the restraint stress-induced inhibition of the LH surge was investigated in the intact cyclic rat. Intracerebroventricular (icv) administration of the GABAA receptor agonist muscimol (0.1, 0.5 or 1 μg) 5 min before the presumed onset of the pro-oestrous LH surge (at 0900 h) caused a dose dependent suppression of the surge. A single dose of the GABAB receptor agonist baclofen (1 μg; icv) injected at 0855 h postponed the onset of the LH surge, and repeated injections at 0855 and 1130 h suppressed the surge. These data indicate that GABA-ergic activity in the brain can inhibit the LH surge in the cyclic rat via GABAA and GABAB receptors. Pro-oestrous rats were subjected to 5 hrs of restraint starting at 0855 h. Pretreatment with the GABAA receptor antagonist bicuculine (1 μg; icv) at 0840, 0940 and 1040 h or pretreatment with the GABAB receptor antagonist phaclofen (10 μg; icv) at 0840 h were ineffective in preventing the restraint-induced inhibition of the LH surge. The results suggest that GABAA and GABAB receptors are not involved in the inhibitory effect of restraint stress on the LH surge.     

Oxytocin links mothering received,mothering bestowed and adult stress responses

We review recent discoveries that implicate oxytocin in the intergenerational transmission of similar levels of maternal behavior and acute stress responses in female rats. First, ICV-infused oxytocin antagonist decreased the display by nursing dams of pup-licking (PL) and arched-back nursing (ABN), but not other components of maternal behavior, and increased maternal self-grooming suggesting that oxytocin may shift the balance of oral grooming by dams away from themselves and toward pups. Second, oxytocin receptor concentrations in areas of the adult brain where oxytocin stimulates maternal behavior or diminishes anxiety and adrenal axis responses to acute stress were positively related to PL-ABN received during infancy. Third, oxytocin and oxytocin antagonist treatments of pups on postnatal days 2-10, respectively increased and decreased PL by the treated rats when adult and themselves nursing dams. This indicates that oxytocin activity in female pups, which may be regulated by PL-ABN received from their mothers, influences their adult levels of PL. These three lines of evidence suggest that oxytocin selectively enhances PL-ABN by rat dams, which then increases oxytocin activity in female pups and, thereby, facilitates their expression of central oxytocin receptors (and perhaps other aspects of central oxytocin systems) and, consequently, their adult PL-ABN frequencies and acute stress responses.     

Post-retrieval effects of icv infusions of hemicholinium in mice are dependent on the age of the original memory

CF-1 male mice were trained in an inhibitory avoidance task using a high footshock (1,2 mA, 50 Hz, 1 sec) in order to reduce the influence of extinction on retention performance. At 2, 7, 14, or 30 d after training, the first retention test was performed and hemicholinium (HC-3, 1.0 microg/mice), a specific inhibitor of high-affinity choline uptake in brain cholinergic neurons, was given intracerebroventricularly immediately after. Twenty four hours after treatment, mice were tested in an inhibitory avoidance task during five consecutive days, each 24 h apart. Retention performance was impaired by HC-3 when the first re-exposure took place at 2, 7, or 14 d, but the effect was no longer seen when re-exposure occurred 30 d after training. We did not find spontaneous recovery 21 d after training, when memory was retrieved 2 d after training and HC-3 was given immediately after. Although we cannot definitively discard a retrieval deficit, this lack of spontaneous recovery is in accordance with the storage-deficit interpretation. These results confirm and extend previous ones, suggesting that central cholinergic mechanisms are involved in the hypothetical reconsolidation memory processes of an inhibitory avoidance task in mice and also suggest that this participation depends on the "age" of the original memory trace. This implies that the vulnerability of a reactivated memory to a specific treatment, as the one used in this study, inversely correlates with the age of the original memory, and it is likely to determine memory reconsolidation processes.     

Behavior and autonomic nervous system function assessed via heart period measures: The case of hyperarousal in boys with fragile X syndrome

Physiological responses may inform us about and help us to interpret behavioral responses. For example, hyperarousal may be a source of behavior problems in children with fragile X syndrome (FXS). To evaluate this approach, we examined heart period data in specific contexts in boys with FXS and in normally developing chronological-age-matched boys. Spectral analysis was used to evaluate the parasympathetic and sympathetic nervous systems’ contributions to heart period. Boys with FXS had shorter interbeat intervals, lower parasympathetic activity, and similar sympathetic activity. Also, the groups were differentially responsive to experimental challenge. These results have important implications for our understanding of the basic nervous system dysfunction in FXS and for the strategies likely to be effective in terms of pharmacological intervention with these children. These methods can be applied to a variety of contexts and populations, including children who are sensory defensive, socially avoidant, inattentive, or hyperactive.     

Involvement of central cholinergic mechanisms in the effects of oxytocin and an oxytocin receptor antagonist on retention performance in mice

Oxytocin (OT, 0.10 microg/kg, sc) impaired retention of a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 10 min after training, as indicated by retention performance 48 h later. In contrast, the immediate post-training administration of the putative oxytocin receptor antagonist d(CH(2))(5)[Tyr(Me)(2), Thr(4), Thy-NH(9)(2)] OVT (AOT, 0.30 microg/kg, sc) significantly enhanced retention performance. Neither OT nor AOT affected response latencies in mice not given footshock on the training trial, and neither the impairing effects of OT nor the enhancing effects of AOT were seen when the training-treatment interval was 180 min, suggesting that both treatments influenced memory storage. The effects of OT (0.10 microg/kg, sc) on retention were prevented by AOT (0.03 microg/kg, sc) given immediately after training, but 10 min prior to OT treatment. The central acting anticholinesterase physostigmine (35, 70, or 150 microg/kg, i.p.), but not its quaternary analogue neostigmine (150 microg/kg, i.p.), reversed the impairment of retention performance induced by OT, whereas low subeffective doses of the centrally active muscarinic cholinergic antagonist atropine (0.5 mg/kg, i.p.) or the central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg, i.p.), but not methylatropine (0.5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.) prevented the enhancement of retention performance caused by AOT. We suggest that oxytocin negatively modulates the activity of central cholinergic mechanisms during the posttraining period that follows an aversively motivated learning experience, leading to an impairment of retention performance of the inhibitory avoidance response.     

Why do you like Arcimboldo’s portraits? Effect of perceptual style on aesthetic appreciation of ambiguous artworks

Visual aesthetic experience reflects the states of the mind and the brain when visual artworks are being viewed. In the present study, we investigated whether perceptual style affects the aesthetic appreciation of ambiguous artworks, such as those of Arcimboldo, which are characterized by part–whole ambiguity. Participants were classified as having a global or local perceptual style and were asked to aesthetically judge two different types of artworks: portraits by Arcimboldo and by Renaissance painters. We found that perceptual style affected both the aesthetic appreciation and the degree of perceived ambiguity in Arcimboldo’s artworks. Our findings suggest that aesthetic judgment is a consequence of the interaction between individual personal perceptual style and the perceptual features of artworks.     

Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation

It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the α(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8μg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia.     

Neuropsychology of Environmental Navigation in Humans: Review and Meta-Analysis of fMRI Studies in Healthy Participants

In the past 20 years, many studies in the cognitive neurosciences have analyzed human ability to navigate in recently learned and familiar environments by investigating the cognitive processes involved in successful navigation. In this study, we reviewed the main experimental paradigms and made a cognitive-oriented meta-analysis of fMRI studies of human navigation to underline the importance of the experimental designs and cognitive tasks used to assess navigational skills. We performed a general activation likelihood estimation (ALE) meta-analysis of 66 fMRI experiments to identify the neural substrates underpinning general aspects of human navigation. Four individual ALE analyses were performed to identify the neural substrates of different experimental paradigms (i.e., familiar vs. recently learned environments) and different navigational strategies (allocentric vs. egocentric). Results of the general ALE analysis highlighted a wide network of areas with clusters in the occipital, parietal, frontal and temporal lobes, especially in the parahippocampal cortex. Familiar environments seem to be processed by an extended temporal-frontal network, whereas recently learned environments require activation in the parahippocampal cortex and the parietal and occipital lobes. Allocentric strategy is subtended by the same areas as egocentric strategy, but the latter elicits greater activation in the right precuneus, middle occipital lobe and angular gyrus. Our results suggest that different neural correlates are involved in recalling a well-learned or recently acquired environment and that different networks of areas subtend egocentric and allocentric strategies.     

Reactivated memory of an inhibitory avoidance response in mice is sensitive to a nitric oxide synthase inhibitor

It is accepted that once consolidation is completed memory becomes permanent. However, it has also been suggested that reactivation (retrieval) of the original memory, again, makes it sensitive to the same treatments that affect memory consolidation when given after training. Previous results demonstrated that the immediate post-training intraperitoneal administration of N^ω-nitro-l-arginine methyl ester (L-NAME), a non-specific inhibitor of nitric oxide synthase (NOS), impairs retention test performance of a one-trial step-through inhibitory avoidance response in adult mice. The effect of L-NAME on retention was attributed to an action on memory consolidation of the original learning. For the first time, we report that the administration of L-NAME after the first retention test (memory reactivation) of the inhibitory avoidance response impairs retention performance over six consecutive days. This impairment effect is dose-and-time dependent and could not be attributed to a retrieval deficit since a mild footshock did not reinstate the original avoidance response and no spontaneous recovery was observed at least 21 days after training. Further support for a storage deficit interpretation as opposed to a retrieval deficit was obtained from the fact that L-NAME’s effects after retrieval were not due to state-dependency. The impairment effect of L-NAME was dependent on the age of the original memory. That is, there was an inverse correlation between the susceptibility of the memory trace when reactivated and the time elapsed between training and the first retrieval session. We suggest an action of L-NAME on memory reactivation-induced processes that are different from memory extinction of the original learning extending the biological significance of nitric oxide on memory.     

Involvement of the basolateral amygdala in muscarinic cholinergic modulation of extinction memory consolidation

Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the involvement of muscarinic cholinergic influences within the BLA in modulating the consolidation of CFC extinction memory. Male Sprague Dawley rats implanted with unilateral cannula aimed at the BLA were trained on a CFC task, using footshock stimulation, and 24 and 48 h later were given extinction training by replacing them in the apparatus without footshock. Following each extinction session they received intra-BLA infusions of the cholinergic agonist oxotremorine (10 ng). Immediate post-extinction BLA infusions significantly enhanced extinction but infusions administered 180 min after extinction training did not influence extinction. Thus the oxotremorine effects were time-dependent and not attributable to non-specific effects on retention performance. These findings provide evidence that, as previously found with original CFC learning, cholinergic activation within the BLA modulates the consolidation of CFC extinction.