Recent evidence suggests that liking and wanting of food rewards can be experimentally dissociated (e.g., Berridge, 1996); this dissociation extends to attenuated neophobia in the present study. Rats tend to eat less of a novel food than a familiar food, a phenomenon called neophobia. The present experiments evaluated whether attenuation of neophobia by prior exposure reflects enhanced liking of the flavor using the Taste Reactivity (TR) test. In Experiment 1, rats given five 10 sec TR trials with water or various concentrations of saccharin solution (0.1%, 0.2%, 0.5%) did not show a change in the number of hedonic reactions displayed across trials. However, in a subsequent consumption test from a bottle containing 0.25% saccharin solution, rats with no prior saccharin exposure (group water) consumed less than rats with prior saccharin exposure; that is they displayed neophobia. In Experiment 2, whether rats received five 10 sec TR trials with water or 0.5% saccharin solution, they did not display a difference in hedonic reactions to 0.25% saccharin solution in two 5 min TR test trials. These results suggest that the attenuation of neophobia is evidenced as an increase in the tendency to approach a bottle containing the flavored solution (wanting), but not as an enhanced liking of that solution.
Taste reactivity; neophobia; palatability; taste; latent inhibition; rat
This study investigated the effects of chronic restraint stress and repeated cyclic estradiol pulses on hippocampal CA3 and CA1 dendritic and/or spine morphology and spatial memory in female rats. Sprague-Dawley adult female rats were ovariectomized and then injected over two days with 17β-estradiol (10µg, s.c.), which was repeated every 4–5 days. While all rats received similar estradiol injection histories, half of the rats were chronically restrained and/or given a final cyclic pulse of estradiol prior to testing on a hippocampal-dependent object placement (OP) task to assess spatial memory. OP testing was performed two days after the last restraint session, as well as when the last two estradiol pulses best captured the maximal effect on hippocampal CA1 spine density. The data revealed several novel findings: 1) chronic stress or estradiol separately facilitated spatial memory, but did not have the same effects when co-administered, 2) CA1 spine densities negatively correlated with spatial memory, and 3) repeated estradiol pulses failed to prevent stress-induced CA3 dendritic retraction. We also corroborated previous studies showing increased CA1 spine density following estradiol, chronic stress, and behavioral manipulations. The present study uniquely combined chronic stress, repeated estradiol pulses, hippocampal morphology and behavior within the same animals, allowing for correlational analyses to be performed between CA1 spine morphology and spatial memory. We demonstrate novel findings that chronic stress or estradiol pulses independently facilitate spatial memory, but not when co-administered, and that these effects may involve a balance of CA1 apical spine expression that is independent of CA3 dendritic complexity.
stress; estradiol; spatial memory; hippocampus; object placement
Exposure to Bisphenol-A (BPA), an endocrine disruptor used in plastics, occurs in the United States on a daily basis. Recent studies suggest exposure during development causes memory deficits later in life, however the ramifications of exposure in adulthood are unclear. We examined the effects of acute BPA administration (40μg/kg) on memory and synaptic plasticity in adult male rats. BPA significantly impaired both visual and spatial memory and decreased dendritic spine density on pyramidal cells in CA1 and the medial prefrontal cortex (mPFC). Additionally, BPA significantly decreased PSD-95, a synaptic marker, in the hippocampus and increased cytosolic pCREB, a transcription factor, in mPFC. Together, these findings show that a single dose of BPA, below the U.S.E.P.A. reference safe daily limit of 50 ug/kg/day, may block the formation of new memories by interfering with neural plasticity processes in the adult brain.
Bisphenol-A; endocrine disruptor; memory; synaptic plasticity
Because no organism lives in an unchanging environment, sensory processes must remain plastic so that in any context, they emphasize the most relevant signals. As the behavioral relevance of sociosexual signals changes along with reproductive state, the perception of those signals is altered by reproductive hormones such as estradiol (E2). We showed previously that in white-throated sparrows, immediate early gene responses in the auditory pathway of females are selective for conspecific male song only when plasma E2 is elevated to breeding-typical levels. In this study, we looked for evidence that E2-dependent modulation of auditory responses is mediated by serotonergic systems. In female nonbreeding white-throated sparrows treated with E2, the density of fibers immunoreactive for serotonin transporter innervating the auditory midbrain and rostral auditory forebrain increased compared with controls. E2 treatment also increased the concentration of the serotonin metabolite 5-HIAA in the caudomedial mesopallium of the auditory forebrain. In a second experiment, females exposed to 30 min of conspecific male song had higher levels of 5-HIAA in the caudomedial nidopallium of the auditory forebrain than birds not exposed to song. Overall, we show that in this seasonal breeder, (1) serotonergic fibers innervate auditory areas; (2) the density of those fibers is higher in females with breeding-typical levels of E2 than in nonbreeding, untreated females; and (3) serotonin is released in the auditory forebrain within minutes in response to conspecific vocalizations. Our results are consistent with the hypothesis that E2 acts via serotonin systems to alter auditory processing.
5-HT; 5-HIAA; estradiol; serotonin transporter (SERT); songbird
The basolateral complex of the amygdala (BLA) modulates memory for emotional events, and direct activation of the BLA following a learning session can enhance subsequent memory. Yet optimal enhancement of episodic memory during emotional events would likely require that BLA activation occur close in time to the event and to be brief enough to target specific memories if some events are to be remembered better than others. In the present study, rats were given a novel object recognition memory task in which initial encounters with some of the objects were immediately followed by brief electrical stimulation of the BLA, and these objects were remembered better one day later as compared to objects for which the initial encounter was not followed by stimulation. The results indicated that BLA stimulation can enhance memory for individual events, a necessary ability for the BLA to modulate episodic memory effectively.
basolateral amygdala; electrical stimulation; object recognition memory; memory enhancement; rat
The catechol-O-methyltransferase (COMT) val158met polymorphism has received attention in schizophrenia due to its role in prefrontal dopamine catabolism. Given the rich dopaminergic innervations of the olfactory bulb and the influence of dopamine on the transmission of olfactory signals, we examined the influence of COMT genotype status on the olfactory processing impairment observed in schizophrenia. The University of Pennsylvania Smell Identification Test was administered unirhinally to individuals with schizophrenia (n = 42) and a demographically-matched sample of healthy controls (n = 30). Individuals were genotyped for the COMT val158met polymorphism. A statistically significant interaction of diagnosis and COMT genotype was observed, such that schizophrenia heterozygotes and Met homozygotes showed impaired odor identification accuracy relative to Val158 homozygotes. These findings could not be explained by factors such as antipsychotic medication status, clinical symptomatology, or demographic and illness characteristics. Notably, the schizophrenia Val158 homozygotes’ odor identification performance was comparable to that of the control group. These data indicate that odor identification impairments observed in schizophrenia are influenced by the COMT val158met polymorphism. This relationship is consistent with specific dopaminergic modulation of primary olfactory sensory afferents, rather than a broader effect on cognitive processes. Future studies examining the olfactory processing deficit in schizophrenia with respect to other olfactory measures and COMT haplotypes is warranted.
dopamine; olfaction; smell; COMT; genetics
Studies have shown that ovarian hormones protect against some of the cognitive deficits associated with aging. Although much of the literature in rodents has focused on hippocampal dependent tasks, studies suggest that tasks dependent on the prefrontal cortex are also influenced by ovarian hormones. The present study investigated the effects of ovarian hormone treatment during aging on a delayed alternation t-maze. Female Long Evans hooded rats were ovariectomized at middle age (11–12 months) and placed in one of 5 treatment groups: no replacement, chronic estradiol (E2), cyclic E2, chronic E2 and progesterone, or chronic E2 and medroxyprogesterone acetate (MPA). Following six months of hormone treatment, animals were trained to alternate in a t-maze. After reaching criterion, a series of delays from 5 to 90 seconds were introduced in random order. Rats receiving E2 with MPA reached criterion significantly faster than animals not receiving treatment and those who received chronic or cyclic E2 only. There was a nonsignificant trend for animals receiving E2 and progesterone to reach criterion in fewer sessions than animals receiving E2 only. Mode of administration, cyclic or chronic, did not affect performance. Hormones did not affect performance on the delayed alternation. This study, in combination with previous research, indicates that hormone effects cannot be generalized across tasks, age or duration, and long-term estrogen in combination with MPA can be beneficial for some tasks.
aging; t-maze; MPA; progesterone; memory
There is considerable controversy about the origins of sex differences in cognitive abilities, particularly the male superiority in spatial abilities. We studied effects of early androgens on spatial and mechanical abilities in adolescents and young adults with congenital adrenal hyperplasia (CAH). On tests of 3D mental rotations, geography, and mechanical knowledge, females with CAH scored higher than their unaffected sisters, and males with CAH scored lower than their unaffected brothers. Exploratory regression analyses suggest that androgens affect spatial ability in females directly and through male-typed activity interests. Findings indicate that early androgens influence spatial and mechanical abilities, and that androgen effects on abilities may occur in part through effects on sex-typed activity interests.
spatial ability; mental rotation; mechanical ability; geography; cognition; sex typing; gender typing; sex differences; androgens; sex hormones; congenital adrenal hyperplasia
Systemic injections of an NMDA antagonist have been shown to impair mating in male rats. One site where glutamate and its NMDA receptors may contribute to mating is the medial preoptic area (MPOA), which is vital for male sexual behavior. Glutamate is released in the MPOA during copulation, and especially at the time of ejaculation. We report here that the NMDA antagonist MK-801, microinjected into the MPOA, impaired copulatory behavior in sexually naïve as well as experienced males. In animals tested both as naïve and after sexual experience, drug treatment produced more profound impairment in naïve males. In addition, MK-801, microinjected into the MPOA before each of 7 noncopulatory exposures to receptive female rats, resulted in copulatory impairments on a drug-free test on day 8, relative to aCSF-treated animals; their behavior was similar to that of males that had not been pre-exposed to females. Therefore, NMDA receptors in the MPOA contribute to the control of copulation and stimulus sensitization. Glutamate, acting via NMDA receptors, regulates many neural functions, including neuronal plasticity. This is the first demonstration that a similar mechanism in the MPOA sensitizes male rats to the stimuli from a receptive female, and thereby enhances their behavior.
Sexual behavior; Medial Preoptic Area; glutamate; NMDA; MK-801; Dizocilpine
Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1. Local estradiol action within an auditory area is necessary for socially-relevant sounds to induce normal physiological responses in the brains of both sexes; 2. These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3. Estradiol action within the auditory forebrain enables behavioral discrimination among socially-relevant sounds in males; and 4. Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors. Keywords: Estrogens, Songbird, Social Context, Auditory Perception
Women experience profound hormonal fluctuations throughout their reproductive lives. They are especially susceptible to disturbances in mood and cognition during the transition from pregnancy into postpartum and motherhood (Brummelte & Galea, 2010). Their behavioral and hormonal responses to stressful stimuli are also altered during this time. These changes are not limited to humans but occur in many mammalian species. Virgin female rats express a severe learning deficit in associative eyeblink conditioning after a stressful life event (Wood & Shors, 1998; Wood et al., 2001), but lactating females or those that are caring for young learn well even after the stressor (Leuner & Shors, 2006). However, we do not know whether maternal experience persistently alters learning after a stressful event. Here we hypothesized that females that had been maternal at some time in their lives would learn well even after exposure to a stressful event. To test this hypothesis, females that had at least one brood of young and expressed a normal estrous cycle were exposed to an acute stressful event that reliably impairs learning in virgin females. Animals were trained 24 h later with classical eyeblink conditioning. Exposure to the stressor suppressed learning in virgins but not in females that had been mothers at some time in their lives. These data suggest that maternal experience induces a protective mechanism in mothers, which promotes associative learning long after the offspring have left their care.
acute stress; maternal experience; eyeblink conditioning; postpartum
A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women.
Estradiol; ERK; PI3K; epigenetic; aging
From its origins in how the brain controls the endocrine system via the hypothalamus and pituitary gland, neuroendocrinology has evolved into a science that now includes hormone action on many aspects of brain function. These actions involve the whole central nervous system and not just the hypothalamus. Advances in our understanding of cellular and molecular actions of steroid hormones have gone beyond the important cell nuclear actions of steroid hormone receptors to include signaling pathways that intersect with other mediators such as neurotransmitters and neuromodulators. This has, in turn, broadened the search for and identification of steroid receptors to include non-nuclear sites in synapses, dendrites, mitochondria and glial cells, as well as cell nuclei. The study of estrogen receptors and estrogen actions on processes related to cognition, mood, autonomic regulation, pain and neuroprotection, among other functions, has led the way in this new view of hormone actions on the brain. In this review we summarize past and current work in our laboratory on this topic. This exciting and growing field involving many laboratories continues to reshape our ideas and approaches to neuroendocrinology both at the bench and the bedside.
estrogens; progesterone; rapid non-genomic actions; hippocampus; cognition; mood; autonomic regulation
Central cannabinoid receptors are thought to mediate neural oscillations and are localized to brain regions implicated in auditory P50 sensory gating, including the hippocampus and neocortex. The current study therefore examined if neural oscillations evoked by the paired clicks (S1, S2) are associated with impaired P50 gating reported in cannabis users. Seventeen heavy cannabis users and 16 cannabis naïve controls participated. Analyses included P50 amplitudes, and time x frequency analyses examining event-related spectral perturbations (ERSP) and inter-trial coherence (ITC). In agreement with prior studies, cannabis users exhibited reduced P50 gating. The ERSP analysis yielded attenuated high frequency activity in the beta range (13-29 Hz) post-S1 and in the gamma range (30-50 Hz) post-S2 in the cannabis group, compared to the control group. Attenuated ITC was also observed in the cannabis group in the post-S2 theta band (4-7 Hz). Greater levels of cannabis use were positively associated with high P50 ratios and negatively with post-S2 ERSP gamma power. These findings suggest that heavy cannabis use is associated with aberrant beta and gamma activity in the dual-click procedure, which corroborates recent work demonstrating disruption of beta/gamma by cannabinoid receptor (CB1) agonists in a rat analogue of this procedure and highlights the translational potential of the dual-click procedure.
P50; Marijuana; auditory gating; beta; gamma; time-frequency
Binge eating and substance dependence are disorders characterized by a loss of control over consummatory behaviors. Given the common characteristics of these two types of disorders, it is not surprising that the comorbidity between eating disorders and substance abuse disorders is high (20–40%; Conason et al., 2006). It is unknown, however, whether loss of control in one disorder predisposes an individual to loss of control in the other. The present study, therefore, used a rodent model to test whether a history of binge eating would augment subsequent responding for cocaine. Using the limited access protocol described by Corwin et al. (1998), 45 adult male Sprague-Dawley rats were maintained on one of four dietary protocols for a period of six weeks: chow only (Chow; n=9), continuous access to an optional source of dietary fat (Ad Lib; n=12), 1-h access to an optional source of dietary fat daily (Daily; n=12), or 1-h access to an optional source of dietary fat on Monday, Wednesday, and Friday (MWF; n=12). All four groups also had unrestricted access to a nutritionally complete diet of chow and water. Fat-bingeing behaviors developed in the MWF rats, the group with the most restricted access to the optional fat. Thereafter, cocaine-seeking and –taking behaviors were assessed in all rats using a self-administration protocol modified from that described by Deroche-Gamonet et al. (2004), which focus on the motivation for and preoccupation with obtaining and consuming drug (assessed using a progressive ratio (PR) schedule of reinforcement) and persistence in responding for drug during periods of signaled drug non-availability (SNA). Rats with the MWF history tended to take more cocaine late in fixed ratio (FR) training, they persisted in their efforts to obtain cocaine in the face of signaled non-availability, worked harder for cocaine on a PR schedule of reinforcement, and exhibited more goal-directed behavior towards the cocaine-associated operandum. These results demonstrate a link between binge-type intake of fat and the development of drug-seeking and -taking behaviors, suggesting that a history of fat bingeing may predispose individuals to exhibit more robust “addiction-like” behaviors toward a substance of abuse. Thus, it appears that conditions promoting excessive behavior toward one substance (e.g., a palatable fatty food) beget excessive behavior toward another (e.g., cocaine).
addiction; bingeing; cocaine; high-fat diet; self-administration
Neonatal hippocampal damage in rodents impairs medial prefrontal working memory functions. To examine whether similar impairment will follow the same damage in primates, adult monkeys with neonatal hippocampal lesions and sham-operated controls were trained on two working memory tasks. The Session Unique-Delayed Non-Match-to-Sample (SU-DNMS) measures maintenance of information in working memory mediated by the ventral lateral prefrontal cortex. The Object Self-Ordered Task (Obj-SO) measures monitoring of information in working memory mediated by the dorsolateral prefrontal cortex. Adult monkeys with neonatal hippocampal lesions performed as well as sham-operated controls on SU-DNMS at either the 5 or 30s delays, but were severely impaired on the Obj-SO task. These results extend the earlier findings in rodents by demonstrating that early lesions of the hippocampus in monkeys impair working memory processes known to require the integrity of the dorsolateral prefrontal cortex, while sparing lower-order working memory processes, such as recency. Although the present results suggest that the lack of functional hippocampal inputs may have altered the maturation of the dorsolateral prefrontal cortex, future studies will be needed to determine whether the nature of the observed working memory deficit is due to an absence of the hippocampus, a maldevelopment of the dorsolateral prefrontal cortex or both.
neonatal lesion; working memory; dorsolateral prefrontal cortex; schizophrenia
During ingestion of water, chocolate, sucrose, and saccharin, pain-related behaviors are suppressed. This ingestion analgesic effect was reversed when the hedonic valence of a food is switched from good to “bad” as occurs during conditioned taste aversion. Here, we tested the converse hedonic shift to determine if ingestion analgesia occurs when 0.3 M NaCl is made palatable by inducing a sodium appetite. In Experiment 1, sham- and sodium-depleted rats were tested for paw withdrawal and lick latencies to brief noxious heat during quiet wake and intraoral NaCl ingestion. Only sodium-depleted rats showed a suppression of heat-evoked reactions during NaCl ingestion. In Experiment 2, we tested whether this analgesic effect is mediated by the brainstem nucleus raphe magnus (NRM). Inactivation of NRM with muscimol blocked ingestion analgesia during NaCl ingestion by sodium-depleted rats. This attenuation was not due to a hyperalgesic effect of NRM inactivation. Muscimol microinjections into a nearby region, the nucleus raphe obscurus (NRO), were ineffective. The present findings demonstrate that the internal milieu of an animal can modify ingestion analgesia, and that the analgesia during NaCl ingestion by sodium hungry rats is mediated by NRM.
ingestion; sodium depletion; rostral ventromedial medulla; nociception; muscimol
A deficit in inhibition may underlie some of the symptoms of Attention-deficit/hyperactivity disorder (ADHD), particularly impulsivity. However, the data on inhibitory deficits in children with ADHD are mixed. Moreover, there has been little characterization of inhibitory processes in animal models of ADHD. Pavlov’s conditioned inhibition procedure allows a direct assessment of the inhibitory status of a stimulus via summation and retardation tests. Therefore, in the current study we examined conditioned inhibition in spontaneously hypertensive rats (SHRs), the most well-validated animal model of ADHD. SHRs and Wistar rats were trained in a simultaneous feature-negative discrimination in eyeblink conditioning. Each session consisted of a mixture of two trial types: a tone paired with a periocular stimulation (A+) or a tone and light presented simultaneously without a periocular stimulation (XA−). Both SHRs and Wistars were able to discriminate A+ from XA− trials. In subsequent summation (X presented simultaneously with a different conditioned excitor, B) and retardation (X paired with the periocular stimulation) tests, the presence of inhibition to X was confirmed in both SHRs and Wistars: X reduced responding to B and X was slow to develop excitation when paired with periocular stimulation. These results are the first to demonstrate Pavlovian conditioned inhibition in SHRs and to use a summation and a retardation test to confirm X as a conditioned inhibitor. The data indicate that conditioned inhibition is intact in SHRs, thus inhibitory processes that do not require prefrontal cortex or cerebellum may be normal in this strain.
SHR; eyeblink conditioning; inhibition; feature-negative; ADHD
In humans, stroke or trauma-induced damage to the orbitofrontal cortex (OFC) or medial prefrontal cortex (mPFC) results in impaired cognitive flexibility. Alcoholics also exhibit similar deficits in cognitive flexibility suggesting that the OFC and mPFC are susceptible to alcohol-induced dysfunction. The present experiments investigated this issue using an attention set-shifting assay in ethanol dependent adult male C57BL/6J mice. Ethanol dependence was induced by exposing mice to repeated cycles of chronic intermittent ethanol (CIE) vapor inhalation. Behavioral testing was conducted 72 hours or 10 days following CIE exposure to determine whether ethanol-induced changes in OFC-dependent (reversal learning) and mPFC-dependent (set-shifting) behaviors are long-lasting. During early ethanol abstinence (72 hrs), CIE mice showed reduced reversal learning performance as compared to controls. Reversal learning deficits were revealed as greater number of trials to criterion, more errors made and a greater difficulty in performing a reversal learning task relative to baseline performance. Furthermore, the magnitude of the impairment was greater during reversal of a simple discrimination rather than reversal of an intradimensional shift. Reversal learning deficits were no longer present when mice were tested 10 days after CIE exposure suggesting that ethanol-induced changes in OFC function can recover. Unexpectedly, performance on the set-shifting task was not impaired during abstinence from ethanol. These data suggest reversal learning, but not attention set-shifting, is transiently disrupted during short-term abstinence from CIE. Given that reversal learning requires an intact OFC, these findings support the idea that the OFC may be vulnerable to the cognitive impairing actions of ethanol.
reversal learning; attention set-shifting; alcohol dependence; withdrawal; behavioral flexibility
Syrian hamsters readily form dominant-subordinate relationships under laboratory conditions. Winning or losing in agonistic encounters can have striking, long-term effects on social behavior, but the mechanisms underlying this experience-induced behavioral plasticity are unclear. The present study tested the hypothesis that changes in brain-derived neurotrophic factor (BDNF) may at least in part mediate this plasticity. Male hamsters were paired for 15-min using a resident-intruder model, and individuals were identified as winners or losers on the basis of their behavior. BDNF was examined with in situ hybridization 2 hours after treatment during the consolidation period of emotional learning. Losing animals had significantly more BDNF mRNA in the basolateral (BLA) and medial (MeA) nuclei of the amygdala when compared to winning animals as well as novel cage and home cage controls. Interestingly, winning animals had significantly more BDNF mRNA in the dentate gyrus of the dorsal hippocampus (DHPC DG) than did losing animals, novel and home cage controls. No conflict-related changes in BDNF mRNA were observed in several other regions including the bed nucleus of the stria terminalis and central amygdala. Next, we demonstrated that K252a, a Trk receptor antagonist, significantly reduced the acquisition of conditioned defeat when administered within the BLA. These data support a model in which BDNF-mediated plasticity within the BLA supports learning of submission or subordinate social status in losing animals, whereas BDNF-mediated plasticity within the hippocampus may instantiate aspects of winning such as control of a territory in dominant animals.
stress; plasticity; basolateral amygdala; hippocampus; submission
The cognitive control of attention involves maintaining task rules in working memory (or “online”), monitoring reward and error rates, filtering distractors, and suppressing prepotent and competitive responses. Weak attentional control increases distractibility and causes attentional lapses, impulsivity and attentional fatigue. Levels of tonic cholinergic activity (changes over tens of seconds or minutes) modulate cortical circuitry as a function of the demands on cognitive control. Increased cholinergic modulation enhances the representation of cues, by augmenting cue-evoked activity in thalamic glutamatergic afferents, thereby increasing the rate of detection. Such cholinergic modulation is mediated primarily via α4β2* nicotinic acetylcholine receptors. Animal experiments and clinical trials in adult patients with ADHD indicate that attentional symptoms and disorders may benefit from drugs that stimulate this receptor. Tonic cholinergic modulation of cue-evoked glutamatergic transients in prefrontal regions is an essential component of the brain’s executive circuitry. This circuitry model guides the development of treatments of deficits in attentional control.
Attention; Top-down Control; Cognitive Impulsivity; Acetylcholine; Glutamate; Nicotine; Dopamine
Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions.
epinephrine; norepinephrine; basolateral amygdala; acetylcholine; hippocampus; neocortex; caudate nucleus; retrograde amnesia; corticosterone; glucocorticoids; stress hormones; inhibitory avoidance; emotional arousal; memory extinction; memory consolidation; memory retrieval; working
The FVB/N (FVB) mouse has been a popular background strain for constructing transgenic mice. However, behavioral phenotyping of the resultant mice is complicated due to severe visual impairment in the FVB background strain. Previous studies reported cognitive impairments with the FVB strain, suggesting the background as unsuitable for behavioral analysis. In this study, we compared FVB mice to the well characterized C57BL/6 (B6) strain in a battery of hippocampus dependent tasks that had several non-visual cues. The tasks included: trace eyeblink conditioning, spontaneous alternation in the Y-maze, social recognition, trace and contextual fear conditioning, and odor habituation-dishabituation. FVB mice were able to learn all the tasks, often to similar levels as B6 mice. In contrast to previous reports, our data suggest FVB mice are not cognitively deficient with temporal memory tasks when the tasks do not rely heavily upon vision. Thus, the FVB strain may be used as the genetic background for behavioral phenotyping when non-visual hippocampal dependent tasks are utilized.
eyeblink conditioning; fear conditioning; Y-maze; social recognition; habituation-dishabituation
Normal aging causes a decline in object recognition. Importantly, lesions of the perirhinal cortex produce similar deficits and also lead to object discrimination impairments when the test objects share common features, suggesting that the perirhinal cortex participates in perceptual discrimination. The current experiments investigated the ability of young and aged animals to distinguish between objects that shared features with tasks with limited mnemonic demands. In the first experiment, young and old rats performed a variant of the spontaneous object recognition task in which there was a minimal delay between the sample and the test phase. When the test objects did not share any features (‘Easy’ perceptual discrimination) both young and aged rats correctly identified the novel object. When the test objects contained overlapping features, however, only the young rats showed an exploratory preference for the novel object. In Experiment 2, young and aged monkeys were tested on an object discrimination task. When the object pairs were dissimilar, both the young and aged monkeys learned to select the rewarded object quickly. In contrast, when LEGOs® were used to create object pairs with overlapping features, the aged monkeys took significantly longer than did the young animals to learn to discriminate between the rewarded and the unrewarded object. Together, these data indicate that behaviors requiring the perirhinal cortex are disrupted in advanced age, and suggest that at least some of these impairments may be explained by changes in high-level perceptual processing in advanced age.
aging; dentate gyrus; monkey; object discrimination; rat
The amygdala has been implicated in affective and social processing for more than a century. Animals with damage to the amygdala have altered affective and social behavior patterns, though the precise nature of these behavioral changes depends on a number of factors including lesion technique, age of the subject at the time of lesion, rearing, and housing environments. Interpretations of amygdala lesion studies are further complicated by the potentially confounded nature of affective and social stimuli (e.g., social interactions with a conspecific partner that is consistently aggressive). In the present study, we evaluated affective responding to socially and emotionally evocative video stimuli in a group of rhesus macaques that received bilateral amygdala lesions as neonates. The stimuli were produced in order to vary independently in terms of their affective and social content. The responses of the amygdala-lesioned animals were compared to a group of age-matched controls and a group of animals that had sustained bilateral hippocampus damage as neonates. As compared to control animals, amygdala-lesioned animals had blunted responding to both positive and negative stimuli, regardless of social content, but did differentiate between categories of social content. Taken together, these findings suggest that early amygdala damage permanently compromises affective processing while leaving intact the ability to distinguish between socially meaningful contexts.
amygdala; hippocampus; affect; emotion; nonhuman primate; Macaca mulatta; rhesus