Norma Serafín

Corticosterone infused into the dorsal striatum selectively enhances memory consolidation of cued water-maze training

Glucocorticoid hormones enhance memory consolidation of hippocampus-dependent spatial/contextual learning, but little is known about their possible influence on the consolidation of procedural/implicit memory. Therefore, in this study we examined the effect of corticosterone (2, 5, or 10 ng) infused into the dorsal striatum of male Wistar rats immediately after training on either a cued or spatial version of the water maze. We found that corticosterone dose-dependently enhanced 48-h retention of the cued training without affecting the retention of the spatial training. These findings indicate that corticosterone acts within the dorsal striatum to enhance memory consolidation of procedural/implicit training.

Sensory and physiological determinants of maternal behavior in the goat (Capra hircus)

Maternal behavior in the goat appears at the time of parturition, partly under the activating influence of vaginocervical stimulation. Mothers actively lick their neonate and rapidly establish a selective bond with their kid through olfactory recognition. They also develop visual and acoustic recognition of the kid within 4 h following birth. Acoustic recognition is present at 48 h. The establishment of maternal recognition can be impaired by underfeeding during the second half of pregnancy. There is no indication that the mechanisms controlling the onset of maternal behavior and bonding are different from those reported in sheep, despite the fact that lambs start to follow their mother within a few hours after birth and kids hide for about a week. During lactation, the cues provided by the kid are necessary for the maintenance of maternal responsiveness, but suckling itself does not appear of primary importance. The presence of the kid also modulates the hormonal response to udder stimulation and influences recovery of postpartum sexual activity when kidding (i.e. birthing) takes place in autumn. Finally, the rapid establishment of mutual attachment between mother goats (does) and their kids offers the possibility to investigate an aspect of mother-young affiliation that is not present in many laboratory species.

Maternal Olfaction Differentially Modulates Oxytocin and Prolactin Release during Suckling in Goats

In postparturient goats, olfactory recognition of the young allows the establishment of a selective bond between the mother and her kids. Once this bond is formed, the mother rejects alien young that attempt to suckle. We tested whether the development of the maternal selective bond in goats modulates prolactin (PRL) and oxytocin (OT) release in response to suckling. On day 37 of lactation, serial blood samples were taken during nursing of the mothers own or alien kid(s) in 10 intact/selective goats and in 10 goats rendered anosmic/nonselective through prepartum peripheral ZnSO(4) irrigation. Spontaneous nursing behavior was also studied weekly from day 7 to 30 of lactation, at which time milk production was measured. Maternal selectivity had no effect on PRL release, in contrast to OT release, which was significantly affected by this factor. Intact mothers released OT only when nursing their own kids, but not with aliens, while anosmic/nonselective dams showed an increase in OT levels regardless of the identity of the kids. In addition to these effects on maternal selectivity, the amplitude of the response of both hormones was lower in anosmic mothers than in intact mothers. Finally, nursing behavior and milk production were not significantly affected by anosmia. We conclude that maternal selective behavior in goats, which relies on the individual olfactory signature of the kid, modulates the OT, but not the PRL, response to suckling. In addition, perception of the smell of the young appears to have a general facilitatory effect, independent of the kids identity, on the release of both hormones.

Glucocorticoids in the dorsomedial striatum modulate the consolidation of spatial but not procedural memory.

Glucocorticoid hormones are known to influence widely interconnected brain networks, thereby enhancing the consolidation of memory of several types of training experiences. In this network, the dorsal striatum plays an important role in transforming goal-directed behavior into habitual behavior. Many studies have shown that the dorsolateral striatum (DLS) enables the formation of stimulus-response associations that are needed for procedural learning. In contrast, the dorsomedial striatum (DMS) is predominantly involved in influencing goal-directed behaviors via interactions with the dorsal hippocampus and medial prefrontal cortex. To date, most studies that have supported a functional dissociation of the dorsal striatum in memory have focused on the behavioral deficits produced by lesions or temporary inactivation of different striatal regions. Few studies have investigated the effect of pharmacological activation of the DMS in modulating memory of distinct kinds of spatial navigation. Therefore, in the present study corticosterone (CORT) was administered into the DMS immediately after training on either a place or cue water-maze task to investigate possible effects on the consolidation of spatial and procedural memory. Our findings indicate that CORT (5, 10 and 20 ng) enhanced 24-h retention of place training, without affecting retention of cue training. However, CORT administration after place and cue training did not shift the selection from a procedural to a spatial navigation strategy in a place-cue competition test. These findings support the functional heterogeneity of the dorsal striatum and suggest that the DMS can modulate the consolidation of allocentric spatial information via glucocorticoid action.

Glucocorticoid-cholinergic interactions in the dorsal striatum in memory consolidation of inhibitory avoidance training

Extensive evidence indicates that glucocorticoid hormones act in a variety of brain regions to enhance the consolidation of memory of emotionally motivated training experiences. We previously reported that corticosterone, the major glucocorticoid in the rat, administered into the dorsal striatum immediately after inhibitory avoidance training dose-dependently enhances memory consolidation of this training. There is also abundant evidence that the intrinsic cholinergic system of the dorsal striatum is importantly involved in memory consolidation of inhibitory avoidance training. However, it is presently unknown whether these two neuromodulatory systems interact within the dorsal striatum in the formation of long-term memory. To address this issue, we first investigated in male Wistar rats whether the muscarinic receptor agonist oxotremorine administered into the dorsal striatum immediately after inhibitory avoidance training enhances 48 h retention of the training. Subsequently, we examined whether an attenuation of glucocorticoid signaling by either a systemic administration of the corticosterone-synthesis inhibitor metyrapone or an intra-striatal infusion of the glucocorticoid receptor (GR) antagonist RU 38486 would block the memory enhancement induced by oxotremorine. Our findings indicate that oxotremorine dose-dependently enhanced 48 h retention latencies, but that the administration of either metyrapone or RU 38486 prevented the memory-enhancing effect of oxotremorine. In the last experiment, corticosterone was infused into the dorsal striatum together with the muscarinic receptor antagonist scopolamine immediately after inhibitory avoidance training. Scopolamine blocked the enhancing effect of corticosterone on 48 h retention performance. These findings indicate that there are mutual interactions between glucocorticoids and the striatal cholinergic system in enhancing the consolidation of memory of inhibitory avoidance training.

Differential effects of undernutrition during pregnancy on the behaviour of does and their kids at parturition and on the establishment of mutual recognition

We investigated whether undernutrition during the second half of pregnancy impaired the behaviour of does and their kids at parturition and early mutual recognition. Twenty-two control and 22 underfed mixed-breed, multiparous dairy goats were used, together with their respective kids (control, n = 31: nine singles, 16 twins and six triplets; underfed, n = 32: 11 singles, 18 twins and three triplets). Undernutrition involved limiting protein and energy intake at 70% of the nutritional requirements for maintenance and foetal growth from day 70 of pregnancy until birth. The behaviour of mothers and their two first-born kids was observed for 90 min from the birth of each kid. Maternal olfactory recognition of the kid was assessed at 4 h post partum by testing selective nursing behaviour. Non-olfactory recognition was assessed at 8 h in a two-choice test excluding olfactory cues. In kids, preference for the mother was assessed in a two-choice test at either 12 or 24 h post partum. Bodyweight of does and kids were lower in the underfed group up to 2 weeks post partum. At parturition, licking, maternal bleating frequency and latency to nursing did not differ between nutritional groups. Control kids were faster than underfed kids to stand, search for and reach the udder, but underfed kids bleated more and tended to spend more time at the udder. Both control and underfed does accepted their own kid and rejected the alien in the selectivity test at 4 h. In contrast, at 8 h post partum, only control goats showed a significant preference for their own kid in the non-olfactory recognition test. Both control and underfed kids showed a preference for their own mother at 12 and 24 h and undernutrition during pregnancy had little influence on the performance of kids. However, 12 h-old underfed kids tended to be less active than control kids and visited their own mothers less than control kids. There were no significant correlations between the behaviour of the mother or of the kid at parturition and their performance in the discrimination tests. Overall, undernutrition in the second half of pregnancy appears to be more detrimental for the behaviour of the mother than for the kid. Furthermore, it has more impact on the establishment of maternal non-olfactory recognition than on maternal care at parturition or the establishment of maternal selectivity.

Acquisition and retention of enhanced active avoidance are unaffected by interference with serotonergic activity.

Pre-training administration of p-chloroamphetamine (PCA) produces reliable deficits of avoidance learning. When animals are trained in inhibitory avoidance with relatively high foot-shock intensities, other amnesic treatments have no effect. The present experiment was conducted to determine if this protective effect of high foot shock is also observed after administration of PCA (10mg/kg, i.p., injected 7 days before training; this dose produces a lesion of central serotonin neurons). Rats were trained in active avoidance (a single 20-trial session), administering shocks of 0.6, 0.8, 1.0, or 1.4 mA to independent groups of rats. When compared to saline-injected groups trained with the same intensities, PCA produced a significant learning deficit in the low foot-shock groups, but not in the high foot-shock animals. These results indicate that the dose of PCA administered, which is known to deplete cerebral serotonin, does not interfere with acquisition and retention of enhanced active avoidance training.

Glucocorticoid administration into the dorsolateral but not dorsomedial striatum accelerates the shift from a spatial toward procedural memory

HIGHLIGHTSCorticosterone administration into the DLS enhances procedural memory in a cross maze.This memory enhancement accelerates the use of a response strategy to solve the task.Corticosterone in the DMS does not alter the switch from place to response strategy.Corticosterone does not affect the overall rate of task acquisition. ABSTRACT Glucocorticoid stress hormones are known to enhance the consolidation of hippocampus‐dependent spatial and contextual memory. Recent findings indicate that glucocorticoids also enhance the consolidation of procedural memory that relies on the dorsal striatum. The dorsal striatum can be functionally subdivided into the dorsolateral striatum (DLS), which is primarily implicated in shaping procedural memories, and the dorsomedial striatum (DMS), which is engaged in spatial memory. Here, we investigated the hypothesis that posttraining glucocorticoid administration into the DLS promotes the formation of a procedural memory that will normally take place only with extensive training. Male Wistar rats were trained to find a reward in a cross maze that can be solved through either place or response learning. Rats received four trials per day for 5 days, a probe trial on Day 6, further training on Days 7–13, and an additional probe trial on Day 14. On Days 2–4 of training, they received posttraining infusions of corticosterone (10 or 30 ng) or vehicle into either the DLS or DMS. Rats treated with vehicle into either the DLS or DMS displayed place learning on Day 6 and response learning on Day 14, indicating a shift in control of learned behavior toward a habit‐like procedural strategy with extended training. Rats administered corticosterone (10 ng) into the DLS displayed response learning on both Days 6 and 14, indicating an accelerated shift to response learning. In contrast, corticosterone administered posttraining into the DMS did not significantly alter the shift from place to response learning. These findings indicate that glucocorticoid administration into the DLS enhances memory consolidation of procedural learning and thereby influences the timing of the switch from the use of spatial/contextual memory to habit‐like procedural memory to guide behavior.

Preference of 12-h-old kids for their mother goat is impaired by pre-partum-induced anosmia in the mother

We investigated whether kids were able to discriminate their own mother from an alien one in a two-choice test on the day of birth when they had access to acoustic, visual and olfactory cues from their mother, and whether this discrimination depended on the selective maternal behaviour of the mother (i.e. exclusive nursing of own kids). When given the choice between their own mother and an alien equivalent dam, 8-h-old kids did not show a significant preference for their dam, whereas 12- and 24-h-old kids did. When given the choice between their own and an alien mother that were both non-selective because they had been rendered peripherally anosmic by irrigation of the nostrils with zinc sulphate, 12-h-old kids did not show a significant preference for their mother. These results are similar to those reported in sheep and may suggest that the contrast of behaviour between their own and an alien mother existing in normosmic does is important for discrimination of dams by kids at this age. Finally, testing 8-h-old kids in a smaller enclosure resulted in some improvement of their performance, although they still failed to display a significant preference for their mother. On the whole, kids are able to discriminate between their own and an alien mother goat as early as previously reported in lambs. The impairment of this ability when mothers are anosmic and not selective suggests that acceptance behaviours displayed by the mother may serve as one of the cues orientating the choice of the kid when given the choice between intact mothers. Finally, the present results do not suggest the existence of fundamental differences in the establishment of a preference for the mother between lambs, which are followers, and kids, which are hiders.

Glucocorticoid interactions with the dorsal striatal endocannabinoid system in regulating inhibitory avoidance memory

The endocannabinoid (eCB) system is highly stress sensitive and known to modulate memory formation of emotionally arousing experiences across different corticolimbic structures. eCB signaling within these circuits is also essentially involved in regulating non-genomically mediated glucocorticoid hormone effects on memory. It has long been thought that the dorsal striatum, which plays a major role in procedural memory and habit formation, is considerably less impacted by stressful experiences; however, recent findings indicate that stress and glucocorticoids also affect striatal-dependent memory processes. Yet, to what extent eCB signaling within the dorsal striatum may mediate such glucocorticoid effects on memory consolidation is currently unknown. Here we show, in male Wistar rats, that the cannabinoid agonist WIN55,212-2 administered into the dorsal striatum immediately after an inhibitory avoidance training experience dose-dependently enhanced 48-h retention performance. Conversely, the cannabinoid type 1 receptor (CB1R) antagonist AM251 impaired retention when administered into the dorsal striatum after inhibitory avoidance training. Most importantly, antagonism of striatal CB1R activity with AM251 completely abolished the effect of corticosterone or of the membrane-impermeable ligand corticosterone:BSA administered posttraining into the dorsal striatum or injected systemically on enhancement of inhibitory avoidance memory. Further, suppression of glucocorticoid signaling by systemic injection of the corticosterone-synthesis inhibitor metyrapone also impaired the memory-enhancing effect of intra-striatal WIN55, 212-2 administration. These findings indicate that the eCB system, in close interaction with glucocorticoid signaling, is involved in modulating plasticity changes underlying memory consolidation not only in corticolimbic structures but also within the dorsal striatum.