Extinction in the developing rat: an examination of renewal effects

In the present series of experiments the context-specificity of extinction was examined from a developmental perspective. For postnatal day (PN) 23 rats, renewal of freezing to an aversive odor conditioned stimulus (CS) was observed when rats were conditioned in Context A, extinguished in Context B, and tested in Context A (i.e., ABA renewal). This effect was not observed in PN16 rats, which is consistent with previous studies suggesting that rats < approximately PN20 are impaired in encoding contextual information [i.e., Carew and Rudy [1991]. Developmental Psychobiology, 24, 191-209]. Subsequent experiments demonstrated that for rats conditioned at PN16 and tested at PN23, contextual regulation of extinction performance depended on the age at which extinction occurred. Specifically, ABA renewal was observed in rats given extinction training at PN22 but not in rats given extinction training at PN17. These latter results show that whether or not context regulates the expression of an ambiguous memory is determined by the animal's age when the memory becomes ambiguous.     

Object exploration in the developing rat: Methodological considerations

The current study was conducted to characterize the ontogeny of novel object recognition in rats. Initial testing (Experiment 1) was conducted in a square arena and it was observed that 21‐day‐old animals would often pause in the corners, greatly increasing between‐subject variability and performance in this test. Significantly greater object exploration and less variability were obtained using a circular arena. In Experiment 2, we report object exploration in 21, 35, 42, and 90‐day‐old male and female Sprague‐Dawley rats using a circular arena. The results show that measures of locomotor activity, object exploration, and within session habituation of these behaviors were surprisingly similar across all ages. Gender differences in locomotor activity were not observed until 42 days of age. Reliable recognition memory was observed at all ages. It is concluded that the novel object recognition test appears well suited for use in young rats. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 373–381, 2013     

Latent inhibition of conditioned odor potentiation of startle: a developmental analysis

We conducted a two-part study of age and latent inhibition in the rat. In the first part of the study, rats given odor-shock pairings at 23 or 75 days of age exhibited a potentiated startle response in the presence of the odor the following day. This effect did not occur in rats trained at 16 or 20 days of age. Odor pre-exposure on the day prior to conditioning markedly reduced the odor potentiation of startle effect in 23- and 75-day-old rats but had no effect in 16 and 20-day-olds. In the second part of the study, rats were pre-exposed to the odor at 16 or 20 days of age and then conditioned at 23 days of age. When tested the day after conditioning, these pre-exposed rats exhibited a disruption in the odor potentiation of startle effect. We compare our results with other studies of latent inhibition, and with recent studies on whether conditioned responses are appropriate to the animal's age at training or their age at test.     

Inhibition of the expression of conditioned cardiac responses in the developing rat

It is generally recognized that during development the capacity to express learning in terms of changes in somatomotor activity is evident earlier than the capacity for learned changes in autonomic responding (e.g., heart rate). In this series of experiments, findings indicate that changes in heart rate to a visual conditioned stimulus (CS) paired with a footshock unconditioned stimulus (US) can be observed as early in development in the rat as freezing responses. However, cardiac responses are inhibited from being expressed by preweanlings (but not adults) during CS–US pairings, the time when heart rate responses are often measured. This inhibition appears to arise from US exposure, and dissipates completely within 2 hr of training. These findings are discussed with respect to developmental changes in US-evoked autonomic arousal and response system dissociations. © 1998 John Wiley & Sons, Inc. Dev Psychobiol 33: 221–233, 1998     

Peculiar modulation of taste aversion learning by the time of day in developing rats

The ontogeny of the temporal context modulation of conditioned taste aversion was studied in male Wistar rats using a palatable 1% NaCl solution. A procedure that included two saline preexposures, a single pairing saline‐lithium chloride (0.15 M; 1% b.w.) either at the same or a different time of day of preexposures and a one‐bottle test at the same time than preexposure was applied. Four age groups (PN32, PN48, PN64, and PN100) covering the complete range from adolescence to the adult period were tested. The results showed no effect of a temporal context shift in PN32. A peculiar enhancement of temporal context‐specific saline aversions was exhibited by PN48 and PN64 rats, while the adult typical temporal context specificity of latent inhibition was only evident in PN100 rats. The results are discussed in terms of the peculiar brain functional organization during a protracted adolescence period. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 51: 147–157, 2009     

Amygdaloid inhibition of maternal behavior in the nulliparous female rat

In the first experiment, the effects of lesions of (1) the amygdala, (2) its major efferent projection system, the stria terminalis or (3) other non-limbic brain sites on the induction of maternal behavior in the nulliparous female rat were investigated. Animals sustaining lesions of either the amygdala or the stria terminalis became maternal more rapidly than did control animals. In the second study the effects of lesions to different portions of the amygdala on both maternal and fear responding were investigated. It was found that animals sustaining damage to the corticomedial amygdaloid nuclei became maternal more quickly than did animals sustaining either basolateral amygdaloid damage or no amygdaloid damage. Also in comparison to lesioned controls, animals with lesions of the amygdala showed reduced ‘fearfulness’ on a number of fear-mediated tasks. The third study attempted to interrelate fear responsiveness and maternal behavior by observing nulliparous animals with amygdaloid or stria terminalis lesions for their responses to unfamiliar foster pups placed daily into their preferred nesting quadrant. While control animals actively avoided pups placed into their nest sites (by moving their nest site to another quadrant of the cage), animals with amygdaloid lesions or lesions of the stria terminalis, did not. These results are interpreted to mean that nulliparous females generally do not respond maternally to pups because these females are, in general, more neophobic than parturient females and they tend to find pups and their novel odors, aversive. This aspect of their behavior is likely mediated by the amygdala. These data are discussed in terms of their relevance to the rapid maternal responsiveness normally shown by the female at parturition.     

Monoamine oxidase activity and serotonin metabolism in the rat brain during latent inhibition

Institute of Physiology Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk (Presented by Academician of the Russian Academy of Medical Sciences V. A. Trufakin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 12, pp. 568–570, December, 1992.     

Influence of hypoxia on excitation and GABAergic inhibition in mature and developing rat neocortex

To analyze the functional consequences of hypoxia on the efficacy of intracortical inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), extra- and intracellular recordings were obtained from rat primary somatosensory cortex in vitro. Hypoxia, induced by transient N₂ aeration, caused a decrease in stimulus-evoked inhibitory postsynaptic potentials (IPSPs), followed by a pronounced anoxic depolarization. Upon reoxygenation, the fast (f-) and long-latency (l-) IPSP showed a positive shift in the reversal potential by 24.4 and 14.9 mV, respectively. The peak conductance of the f-and l-IPSP was reversibly reduced in the postanoxic period by 72% and 94%, respectively. Extracellular field potential recordings and application of a paired-pulse inhibition protocol confirmed the enhanced sensitivity of inhibitory synaptic transmission for transient oxygen deprivation. Intracellular recordings from morphologically or electrophysiologically identified interneurons did not reveal any enhanced susceptibility for hypoxia as compared to pyramidal cells, suggesting that inhibitory neurons are not selectively impaired in their functional properties. Intracellularly recorded spontaneous IPSPs were transiently augmented in the postanoxic period, indicating that presynaptic GABA release was not suppressed. Developmental studies in adult (older than postnatal day 28), juvenile (P14–18), and young (P5-8) neocortical slices revealed a prominent functional resistance of immature tissue for hypoxia. In comparison with adult cortex, the hypoxia-induced reduction in excitatory and inhibitory synaptic transmission was significantly smaller in immature cortex. Our data indicate a hypoxia-induced distinct reduction of postsynaptic GABAergic mechanisms, leading to the manifestation of intracortical hyperexcitability as a possible functional consequence.     

NMDA-induced apoptosis in the developing rat brain

The N-methyl-D-aspartate receptor (NMDAR), which is one of the glutamate receptors, is considered to have a close relation to synaptic plasticity in the developing brain. In addition, it is also known that the excessive stimulation of NMDARs can trigger neuronal apoptosis. In this study, we examined the expression of neuronal apoptosis in the developing rat brain after the administration of NMDA to pregnant dams or neonates (embryonal days 18 to postnatal days 14). In the NMDA-treated group, the significant increase in nuclei of apoptotic neuronal cells occurred in the dose-dependent manner in the lateral-ventral regions of the fetal cerebral cortex, reaching maximum values at 24 hours after treatment. On the other hand, the induction of apoptosis did not occur in the neonatal brain.     

Latent learning of spatial information is impaired in middle‐aged rats

The present study determined if the middle age related impairment that occurs with nonspatial latent learning also occurs in spatial latent learning. Thirty young (3‐months‐old) and 30 middle‐aged (12‐months‐old) male Sprague–Dawley rats were given either pre‐exposure to spatial cues surrounding a Barnes maze (SpatialPX), or pre‐exposure to just the maze (MazePX). They were then given 10 training trials in which they had to find a hidden escape box while experiencing an aversive environment produced by bright lights and wind. Results showed that young rats given the SpatialPX condition demonstrated faster escape latencies and fewer errors than young rats given the MazePX condition. However, middle‐aged rats given the SpatialPX condition did not show this improved performance. These findings indicate that the middle age learning deficit is not task specific, but rather is a general impairment in latent learning, possibly due to the early degeneration of the entorhinal cortex. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 309–315, 2013     

Neuraminidase- and benzalkonium chloride-dependent inhibition of basic peptide-induced rat mast cell secretion

Two types of inhibition of basic peptide-induced rat mast cell secretion are reported. Pretreatment of rat peritoneal mast cells with Vibrio comma neuraminidase, an enzyme which cleaves sialic acid from oligosaccharides, led to inhibition of 5-hydroxytryptamine release induced by the basic peptides polylysine, corticotropin_1–24 and a decapeptide sequence of human IgE. Inhibition was similarly observed when mast cells were challenged in the presence of the cationic cell membrane-active substance benzalkonium chloride. It is postulated that both of these experimental procedures inhibit basic peptide-induced secretion by depletion of cell surface negative charge. Sialic acid itself does not act as a specific receptor for basic peptides, since a molar excess of sialic acid in free solution failed to inhibit secretion by binding to basic peptides in the fluid phase.     

Potentiation and inhibition of ultrasonic vocalization of rat pups: Regulation by social cues

Eight- and 11- to 12-day-old rat pups were tested in isolation and in the presence of an anesthetized adult under cold conditions. Pups of both ages reduced rates of ultrasonic vocalization (USV) when an adult was placed into the test cage, independent of whether the adult was their dam or an unrelated male. However, afer removal of the dam, pups greatly increased their rates of USV over their first isolation period and in comparison with control pups. USV rates remained low after removal of the male. The temperature challenges faced by the pups in the two experimental conditions were the same. These phenomena are better explained by a hypothesis that postulates USV rate as being multiply determined, including by social cues, rather than a theory that considers thermal challenge only. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 195–200, 1997     

Renal cortical accumulation of hyaluronan in adult rats exposed neonatally to angiotensin‐converting enzyme inhibition

Neonatal inhibition of the renin–angiotensin system [angiotensin‐converting enzyme (ACE) inhibition] in the rat results in long‐term abnormal renal morphology and function, including interstitial inflammation and fibrosis. Hyaluronan (hyaluronic acid, HA) has pathological implications in inflammatory diseases and renal ischaemia‐reperfusion injury. The present study aimed at determining if renal cortical HA in the adult rat is correlated to the abnormal morphology and function in rats treated neonatally with the ACE inhibitor enalapril. In adult control rats (23 weeks old), the cortical HA content was very low [about 5 μg g^–1 dry weight (d.w.)] and about 1% of the papillary HA content. In rats treated neonatally with enalapril (days 3–13), the cortical HA level was 15 times that in control rats already at 21 days after birth, and it persisted at this level during adulthood (at 23 weeks). At 13 weeks the enalapril‐treated animals showed markedly reduced ability (–53%) to concentrate urine during 24‐h thirst provocation. At 21 days as well as at 23 weeks the enalapril‐treated kidneys displayed morphological changes, such as papillary atrophy, dilation of the tubules and cellular infiltration of the cortical tissue. Histochemical staining confirmed the HA quantification assay and revealed a patchy staining for HA located in the same regions as the infiltrating cells. In conclusion, neonatal treatment with the ACE inhibitor enalapril results in renal morphological and functional abnormalities during adulthood. Cortical HA levels are already seriously elevated at day 21 and coexist with infiltrating cells. Besides the known effects of angiotensin II in development, the accumulation of HA in these kidneys may be involved in the genesis of at least the cortical abnormalities in enalapril‐treated animals because of the proinflammatory effects and water‐binding properties of HA.     

Pharmacological models of the specific role of the dopaminergic and serotoninergic brain systems in latent inhibition

Department of Central Mechanisms of Regulation, Institute of Physiology, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. I. Borodin.) Translated from Byulleten Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 12, pp. 616–617, December, 1990.     

The role of medial prefrontal cortex in context-specific inhibition during reversal learning of a visual discrimination

Rats with medial prefrontal cortex or sham lesions were trained on a visual discrimination task designed for the eight-arm radial maze. After reaching asymptotic performance on this task, both groups were divided into sub-groups that would experience reversal learning in the same or different context from original training. The results showed that both groups reversed in the different context had accelerated learning compared to the groups reversed in the same context. Reversal learning in rats with medial prefrontal cortex damage was faster than sham animals in the same context. These and other results from a transfer test suggest that the medial prefrontal cortex participates in the behavioral effects of a context-specific inhibitory association acquired during visual discrimination learning.     

Transitory subependymal cysts in the developing rat rhombencephalon

Summary A bilaterally symmetrical cystic cavity is situated in the subependymal neuropil of the rostral rhombencephalon of the rat during the perinatal period of ontogeny. These cysts are formed by the confluence of enlarged extracellular spaces in this region between E18 and E20. The cysts are present for about 2 weeks but disappear on about P15 without trace. They have a maximal volume of about 0.004 to 0.006 mm³ on P2, with a rostrocaudal extension of about 200 m. Their shape is characterized by a medial convexity and a lateral concavity, and they have their maximal circumference at about the middle of the rostrocaudal axis. The caudal portion is juxtaposed to the subependyma, while the rostral part lies in the neuropil of the presumptive griseum centrale pontis. In the lumen and the wall of the cysts are found numerous macrophages, hlioblasts and some degenerating axons and dendrites.The significance of these cysts in the context of morphogenesis and the origin of the numerous macrophages within them are both unresolved.