Biomedical subjects

Tracey J Shors

Publications and source records attributed to Tracey J Shors.

At least 19 recordsLinked to original sources

PubMed2006

Temporal discontiguity is neither necessary nor sufficient for learning-induced effects on adult neurogenesis.

Some, but not all, types of learning and memory can influence neurogenesis in the adult hippocampus. Trace eyeblink conditioning has been shown to enhance the survival of new neurons, whereas delay eyeblink conditioning has no such effect. The key difference between the two training procedures is that the conditioning stimuli are separated in time during trace but not delay conditioning. These findings raise the question of whether temporal discontiguity is necessary for enhancing the survival of new neurons. Here we used two approaches to test this hypothesis. First, we examined the influence of a delay conditioning task in which the duration of the conditioned stimulus (CS) was increased nearly twofold, a procedure that critically engages the hippocampus. Although the CS and unconditioned stimulus are contiguous, this very long delay conditioning procedure increased the number of new neurons that survived. Second, we examined the influence of learning the trace conditioned response (CR) after having acquired the CR during delay conditioning, a procedure that renders trace conditioning hippocampal-independent. In this case, trace conditioning did not enhance the survival of new neurons. Together, these results demonstrate that associative learning increases the survival of new neurons in the adult hippocampus, regardless of temporal contiguity.

Animals↗

PubMed2006

Learning during middle age: a resistance to stress?

Acute stressful experience enhances subsequent learning in males and impairs learning in females. These sex differences emerge soon after puberty in adulthood. Whether these opposite effects of stress on learning extend into older age is unknown. To examine this, young adult (2-3 months) and middle aged (17-18 months) Fischer 344 rats of both sexes were exposed to an acute stressor of brief tailshocks and trained 24 h later with classical eyeblink conditioning using a trace paradigm. Whereas stressful experience enhanced conditioning in adult males and impaired conditioning in adult females, it had no effect whatsoever on conditioning in the aging animals of either sex. There was no effect of aging itself on acquisition of the conditioned response, suggesting that trace conditioning is not necessarily compromised during this period of life. Together, these data indicate that associative learning in the aging animal is resistant to both the negative and positive consequences of stressful experience.

Age Factors↗

PubMed2006

Trace conditioning and the hippocampus: the importance of contiguity.

Trace conditioning, a form of classical conditioning in which the presentation of the conditioned stimulus (CS) and the unconditioned stimulus (US) is separated in time by an interstimulus interval, requires an intact hippocampus. In contrast, classical conditioning procedures in which the CS and US are not separated by an interstimulus interval (i.e., delay conditioning procedures) typically do not (Solomon et al., 1986). However, why trace conditioning is dependent on the hippocampus is unknown. Several theories suggest that it is specifically the discontiguity between the CS and US in trace conditioning that critically engages the hippocampus. However, there are other explanations that do not depend on discontiguity. To determine whether the lack of contiguity renders trace conditioning hippocampal dependent, we designed a "contiguous trace conditioning" (CTC) paradigm in which CS-US contiguity is restored by re-presenting the CS simultaneously with the US. Although rats with excitotoxic lesions of the hippocampus could not learn a standard trace fear-conditioning paradigm, lesioned rats trained on CTC showed significant conditioning, at levels similar to those with sham surgeries. Importantly, lesioned rats trained solely with simultaneous CS-US presentations did not demonstrate conditioning. Together, these data suggest that rats with hippocampal lesions can form a memory of a trace CS-US association when contiguity is restored. Therefore, the dependence of traditional trace paradigms on the hippocampus can be attributed to the absence of temporal contiguity.

Animals↗

PubMed2006

Growth hormone is produced within the hippocampus where it responds to age, sex, and stress.

Recent studies by our group and others have demonstrated that growth hormone (GH) is produced endogenously within the hippocampal formation, a brain structure associated with learning and aspects of emotional experience. Here, we demonstrate that this endogenously produced GH is modulated by age and sex differences and the presence of estrogen. GH mRNA levels were higher in females than males, especially during proestrus, a stage of estrus when estrogen levels are elevated. Moreover, GH expression was increased in ovariectomized females that were treated with estradiol. This increase in GH mRNA in response to estrogen was followed by the appearance of GH protein and was negatively correlated with the expression levels of insulin-like growth factor-I mRNA, suggesting a feedback relationship between insulin-like growth factor-I and GH in the brain. GH mRNA levels were also elevated in primary neuronal cultures exposed to 17-beta-estradiol in vitro, further confirming the direct influence of estrogen on GH expression. Finally, exposure to an acute stressful event increased the expression and production of GH in both males and females. However, the stress-induced increase of GH in females depended on the stage of the estrous cycle in which they were exposed to the stressful event. Together, these data further demonstrate that GH is endogenously produced in the adult hippocampal formation, where it is regulated by age, estrogen, and exposure to environmental stimuli. These results suggest that GH may be involved in functions ascribed to the hippocampus, such as learning and the response to stressful experience.

Aging↗

PubMed2006

Learning during motherhood: A resistance to stress.

Hormonal and emotional responses to stress are diminished during pregnancy and the postpartum period. However, the effects of stress on learning during these stages of the female life span have not been examined. In previous studies, we have reported that exposure to an acute stressful event reduces classical eyeblink conditioning 24 h later in adult virgin female rats that are experiencing an ovarian cycle. Here we show that conditioning during late pregnancy was similarly reduced by stressful experience. However, conditioning in postpartum females was unaffected by stressor exposure. The resistance to stress during the postpartum period was evident as early as 2 days after parturition and persisted until the late postpartum period, just prior to weaning. Postpartum conditioning was unresponsive to numerous types of stressors, including brief inescapable tailshocks, swim stress, and exposure to a male intruder. The resistance to stress appears to be dependent on the presence of the offspring, because the impairment in conditioning returned when postpartum females were separated from their pups. Moreover, the resistance to stress occurred in virgin females that behaved maternally after being exposed to young pups for several days. Together, these data suggest that the presence of offspring and the nurturing and care-giving activities that they elicit protect females from the adverse effect of stress on processes involved in learning and memory.

Animals↗

PubMed2006

Is there a link between adult neurogenesis and learning?

During the past several years, evidence has accumulated suggesting a relationship between newly born cells in the hippocampus and various types of learning and memory. However, most of the evidence is correlational and some of it does not agree. This review discusses both sides of this issue, considering the effects of learning on the production of new neurons in the dentate gyrus and the question of whether newly born cells participate in learning and memory.

Animals↗

PubMed2006

Stressful experience and learning across the lifespan.

It is usually assumed that stressful life events interfere with our ability to acquire new information. However, many studies suggest that stressful experience can enhance processes involved in learning. The types of learning that are enhanced after stressful experiences include classical fear and eyeblink conditioning, as well as processes related to learning about threatening stimuli. Stressful life experiences do seem to interfere with processes involved in memory, often expressed as deficits in the retention or retrieval of information that was acquired prior to and was unrelated to the stressful experience. The trends are limited, as are their implications, because most studies examine adult males, yet the effects of stress on learning processes are influenced by age and sex differences. With respect to mechanisms and anatomical substrates, the effects of stress on learning are usually dependent on the action of stress hormones in combination with neuronal activities within the hippocampus, amygdala, the bed nucleus of the stria terminalis, and the prefrontal cortex.

Adult↗

PubMed2005

Significant life events and the shape of memories to come: a hypothesis.

Much has been said about how significant life events modulate our response to stimuli that are integral to those events. However, we know less about the more general consequences of these events, that is, how they affect subsequent learning abilities that are seemingly irrelevant to the initial event. Here, it is proposed that significant life events, most often stressful in nature, alter future learned responses by inducing nonspecific and persistent changes in neuroanatomical structures. These changes are induced in the presence of sex and stress hormones, which are released either in response to the event itself or as a consequence of stages of life. To illustrate, the effects of acute stressful experience on learning processes and their regulation by the release of hormones are reviewed. I discuss how these events and their hormonal consequences alter anatomical substrates such as those involved in neurogenesis and synaptogenesis. It is proposed that these modulatory processes allow past experiences to change the shape of memories to come. In this way, memorable life events become less about the past and more about the future.

Adaptation, Psychological↗

PubMed2005

Distinctive stress effects on learning during puberty.

Puberty is a time of significant change in preparation for adulthood. Here, we examined how stressful experience affects cognitive and related hormonal responses in male and female rats prior to, during and after puberty. Groups were exposed to an acute stressor of brief periodic tailshocks and tested 24 h later in an associative memory task of trace eyeblink conditioning. Exposure to the stressor did not alter conditioning in males or females prior to puberty but enhanced conditioning in both males and females during puberty. The enhancement occurred in pubescent females irrespective of the estrous cycle. In adulthood, sex differences in trace conditioning and the response to stress emerged: females outperformed males under unstressed conditions, but after stressor exposure, trace conditioning in females was impaired whereas that in males was enhanced. These differences were not related to changes in gross motor activity or other nonspecific measures of performance. The effects of acute stress on corticosterone, estradiol, progesterone, and testosterone were also measured. Stressor exposure increased the concentration of corticosterone in all age groups, although sex differences were only evident in adults. All reproductive hormones except estradiol increased with age in a predictable and sex dependent fashion and none were affected by stressor exposure. Estradiol decreased in male rats across age, and remained stable for female rats. Together, these data indicate that males and female respond similarly to learning opportunities and stressful experience before and during puberty; it is in adulthood that sex differences and the opposite responses to stress arise.

Aging↗

PubMed2005

The bed nucleus of the stria terminalis is critically involved in enhancing associative learning after stressful experience.

Exposure to an acute stressful event enhances trace eyeblink conditioning in male rats, even when rats begin training days after the stressor (Shors, 2001). The authors examined whether the bed nucleus of the stria terminalis (BNST), an area involved in stress and anxiety, is critically involved in this effect and, if so, when. The authors found that excitotoxic lesions to the BNST prevented the enhanced conditioning after stressor exposure. In addition, temporary inactivation of the BNST during the stressor did not alter enhanced responding, whereas inactivation during training prevented the enhancement. These data indicate that stressful experience induces persistent changes in the BNST that are necessary for enhancing learning well after the stressful event has ceased.

Analysis of Variance↗

PubMed2004

Males and females respond differently to controllability and antidepressant treatment.

BACKGROUND: Women are much more likely to suffer from stress-related mental illness than men; yet few, if any, animal models for such sex differences exist. Previously, we reported that exposure to an acute stressor enhances learning in male rats yet severely impairs learning in female rats. Here, we tested whether these opposite effects in males versus females could be prevented by establishing control over the stressor or by antidepressant treatment. METHODS: Learning was assessed using the hippocampal-dependent task of trace eyeblink conditioning. In the first experiment, groups of male and female rats were exposed to controllable or uncontrollable stress and trained. In a second experiment, they were exposed to an uncontrollable stressor after chronic treatment with the antidepressant fluoxetine (Prozac). In a final experiment, females were exposed to uncontrollable stress after acute treatment with fluoxetine. RESULTS: Establishing control over the stressful experience eliminated the detrimental effect of stress on learning in females as well as the enhancing effect of stress in males. Moreover, chronic but not acute treatment with fluoxetine prevented the learning deficit in females after exposure to stress. Treatment with fluoxetine did not alter the male response to stress. CONCLUSIONS: These data indicate that males and females not only respond in opposite directions to the same stressful event but also respond differently to controllability and antidepressant treatments.

Analysis of Variance↗

PubMed2004

Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory.

Trace memories are formed when a stimulus event becomes associated with another event that occurs later in time and is discontinuous with the first event. The formation of trace memories enhances the survival of newly generated neurons in the dentate gyrus of the adult hippocampus (Gould et al., 1999a). Here we tested whether the acquisition of trace memories early during training is sufficient to enhance cell survival. We also examined whether the new neurons affected by trace memory formation persist indefinitely or only as long as the hippocampus is necessary for the expression of those memories. Groups of adult rats were injected with bromodeoxyuridine (BrdU), a marker of dividing cells, and trained 1 week later with paired stimuli using a trace eyeblink conditioning task or exposed to the same number of unpaired stimuli. Cell survival was assessed after different numbers of training trials and survival periods after training. Overall cell survival was not enhanced by exposure to 200 trials of paired stimuli during trace conditioning. However, there was a positive correlation between performance of individual animals and cell survival. In addition, exposure to 800 trials of paired stimuli during trace conditioning increased the number of BrdU-labeled cells 60 d after training. The vast majority of these cells were neurons and coexpressed the neuronal markers class IIIbeta-tubulin or neuronal nuclei. These data suggest that individual differences in associative learning predict whether new neurons will survive and that once affected, these neurons remain for months and beyond the time when they are required for the retention of trace memories.

Animals↗

PubMed2004

Acute stress impairs trace eye blink conditioning in females without altering the unconditioned response.

Exposure to an acute stressor of inescapable swimming or intermittent tail shocks impairs classical eye blink conditioning 24h later in female rats. This effect is often attributed to a deficit in "learning," but since stress has been shown to induce analgesia, an alternative explanation is that stressor exposure reduces conditioning by lessening the perceived intensity of the unconditioned stimulus (US). To address this possibility we examined the amplitude of the unconditioned response (UR) during training and found that although exposure to the stressor impaired trace conditioning, there was no difference in the UR amplitude. We also found that eye blink responses to different US intensities (4-12 V) in the absence of training were unaffected by stressor exposure. Taken together, these experiments indicate that the stress-induced impairment of conditioning in females is not due to a decreased perception of US strength.

Analysis of Variance↗

PubMed2004

Memory traces of trace memories: neurogenesis, synaptogenesis and awareness.

To associate events that are disparate in time, the brain must record, retain and perhaps even reflect on the individual events themselves. Aspects of such learning can be probed with trace conditioning, during which an animal learns to associate events that are temporally distant from one another. For decades, we have known that the formation of so-called trace memories (in which one stimulus is associated with a second stimulus that is discontinuous and later in time) depends on the hippocampal formation. Recent findings indicate that the hippocampus is crucial for the initial acquisition of trace memories but not for their expression or long-term storage. More recent findings implicate neurogenesis, synaptogenesis and awareness in the formation of trace memories.

Animals↗

PubMed2004

New spines, new memories.

For more than a century dendritic spines have been a source of fascination and speculation. The long-held belief that these anatomical structures are involved in learning and memory are addressed. Specifically, two lines of evidence that support this claim are reviewed. In the first, we review evidence that experimental manipulations that affect dendritic spine number in the hippocampus also affect learning processes of various sorts. In the second, we review evidence that learning itself affects the presence of dendritic spines in the hippocampus. Based on these observations, we propose that the presence of spines enhances synaptic efficacy and thereby the excitability of the network involved in the learning process. With this scheme, learning is not dependent on changes in spine density but rather changes in the presence of dendritic spines provide anatomical support for the processing of novel information used in memory formation.

Animals↗

PubMed2003

Can new neurons replace memories lost?

It now appears that new neurons are produced not only in the healthy adult brain but also in the brains of patients with Alzheimer's disease (AD). Although the function of new neurons in the healthy brain is unknown, there is evidence that they are involved in certain types of memory formation and that their survival is enhanced dramatically and persistently by learning experiences. The evidence that neurogenesis, or at least the expression of proteins unique to immature neurons, occurs during the late stages of AD raises the possibility that their production could be enhanced earlier in the disease process before so many neurons and memories are lost.

Alzheimer Disease↗

PubMed2003

Brain-derived neurotrophic factor-induced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity.

Synaptic strengthening induced by brain-derived neurotrophic factor (BDNF) is associated with learning and is coupled to transcriptional activation. However, identification of the spectrum of genes associated with BDNF-induced synaptic plasticity and the correlation of expression with learning paradigms in vivo has not yet been studied. Transcriptional analysis of BDNF-induced synaptic strengthening in cultured hippocampal neurons revealed increased expression of the immediate early genes (IEGs), c-fos, early growth response gene 1 (EGR1), activity-regulated cytoskeletal-associated protein (Arc) at 20 min, and the secreted peptide VGF (non-acronymic) protein precursor at 3 hr. The induced genes served as prototypes to decipher mechanisms of both BDNF-induced transcription and plasticity. BDNF-mediated gene expression was tyrosine kinase B and mitogen-activated protein kinase-dependent, as demonstrated by pharmacological studies. Single-cell transcriptional analysis of Arc after whole-cell patch-clamp recordings indicated that increased gene expression correlated with enhancement of synaptic transmission by BDNF. Increased expression in vitro predicted elevations in vivo: VGF and the IEGs increased after trace eyeblink conditioning, a hippocampal-dependent learning paradigm. VGF protein was also upregulated by BDNF treatment and was expressed in a punctate manner in dissociated hippocampal neurons. Collectively, these findings suggested that the VGF neuropeptides may regulate synaptic function. We found a novel function for VGF by applying VGF peptides to neurons. C-terminal VGF peptides acutely increased synaptic charge in a dose-dependent manner, whereas N-terminal peptide had no effect. These observations indicate that gene profiling in vitro can reveal new mechanisms of synaptic strengthening associated with learning and memory.

Animals↗

PubMed2003

Associative memory formation increases the observation of dendritic spines in the hippocampus.

Dendritic spines are sources of synaptic contact that can be altered by experience and, as such, may be involved in memories for that experience. Here we tested whether the acquisition of new memories is associated with changes in the density of dendritic spines. Adult male rats were trained using the trace eyeblink conditioning paradigm, an associative learning task that requires the hippocampus for acquisition. Additional groups were exposed to the same number of stimuli presented in an explicitly unpaired manner or were naive. Twenty-four hours later, the density of dendritic spines was measured using Golgi impregnation. Trace conditioning was associated with an increase in the density of dendritic spines on the pyramidal cells of area CA1 of the hippocampus, an effect that was prevented by blocking acquisition of the learned response with a competitive NMDA receptor antagonist. Training with delay conditioning, a similar task that does not require the hippocampus, also produced an increase in spine density. The learning-induced increase in dendritic spine density was specific to basal dendrites of pyramidal cells in the CA1 region of the hippocampus. Changes did not occur on their apical dendrites or on cells in the dentate gyrus or somatosensory cortex. These results suggest that the formation and expression of associative memories increase the availability of dendritic spines and the potential for synaptic contact.

Animals↗