Neurobehavioral Research Laboratory

Vista Center, NJ, United States

Neurobehavioral Research Laboratory

Vista Center, NJ, United States
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Myers C.E.,Rutgers University | Myers C.E.,Neurobehavioral Research Laboratory | Scharfman H.E.,New York University | Scharfman H.E.,The Nathan Kline Institute for Psychiatric Research
Hippocampus | Year: 2011

Many theories of hippocampal function assume that area CA3 of hippocampus is capable of performing rapid pattern storage, as well as pattern completion when a partial version of a familiar pattern is presented, and that the dentate gyrus (DG) is a preprocessor that performs pattern separation, facilitating storage and recall in CA3. The latter assumption derives partly from the anatomical and physiological properties of DG. However, the major output of DG is from a large number of DG granule cells to a smaller number of CA3 pyramidal cells, which potentially negates the pattern separation performed in the DG. Here, we consider a simple CA3 network model, and consider how it might interact with a previously developed computational model of the DG. The resulting "standard" DG-CA3 model performs pattern storage and completion well, given a small set of sparse, randomly derived patterns representing entorhinal input to the DG and CA3. However, under many circumstances, the pattern separation achieved in the DG is not as robust in CA3, resulting in a low storage capacity for CA3, compared to previous mathematical estimates of the storage capacity for an autoassociative network of this size. We also examine an often-overlooked aspect of hippocampal anatomy that might increase functionality in the combined DG-CA3 model. Specifically, axon collaterals of CA3 pyramidal cells project "back" to the DG ("backprojections"), exerting inhibitory effects on granule cells that could potentially ensure that different subpopulations of granule cells are recruited to respond to similar patterns. In the model, addition of such backprojections improves both pattern separation and storage capacity. We also show that the DG-CA3 model with backprojections provides a better fit to empirical data than a model without backprojections. Therefore, we hypothesize that CA3 backprojections might play an important role in hippocampal function. © 2010 Wiley Periodicals, Inc.

Holloway J.L.,Rutgers University | Trivedi P.,Rutgers Honors College | Myers C.E.,Rutgers University | Myers C.E.,Neurobehavioral Research Laboratory | And 2 more authors.
Frontiers in Behavioral Neuroscience | Year: 2012

In classical conditioning, proactive interference may arise from experience with the conditioned stimulus (CS), the unconditional stimulus (US), or both, prior to their paired presentations. Interest in the application of proactive interference has extended to clinical populations as either a risk factor for disorders or as a secondary sign. Although the current literature is dense with comparisons of stimulus pre-exposure effects in animals, such comparisons are lacking in human subjects. As such, interpretation of proactive interference over studies as well as its generalization and utility in clinical research is limited. The present study was designed to assess eyeblink response acquisition after equal numbers of CS, US, and explicitly unpaired CS and US pre-exposures, as well as to evaluate how anxiety vulnerability might modulate proactive interference. In the current study, anxiety vulnerability was assessed using the State/Trait Anxiety Inventories as well as the adult and retrospective measures of behavioral inhibition (AMBI and RMBI, respectively). Participants were exposed to 1 of 4 possible pre-exposure contingencies: 30 CS, 30 US, 30 CS, and 30 US explicitly unpaired pre-exposures, or Context pre-exposure, immediately prior to standard delay training. Robust proactive interference was evident in all pre-exposure groups relative to Context pre-exposure, independent of anxiety classification, with CR acquisition attenuated at similar rates. In addition, trait anxious individuals were found to have enhanced overall acquisition as well as greater proactive interference relative to non-vulnerable individuals. The findings suggest that anxiety vulnerable individuals learn implicit associations faster, an effect which persists after the introduction of new stimulus contingencies. This effect is not due to enhanced sensitivity to the US. Such differences would have implications for the development of anxiety psychopathology within a learning framework. © 2012 Holloway, Trivedi, Myers and Servatius.

Catuzzi J.E.,Neurobehavioral Research Laboratory | Catuzzi J.E.,Rutgers University | Beck K.D.,Neurobehavioral Research Laboratory | Beck K.D.,Rutgers University
Experimental Neurology | Year: 2014

Females are twice as likely to develop an anxiety disorder compared to males, and thus, are believed to possess an innate vulnerability that increases their susceptibility to develop an anxiety disorder. However, studies using aversive learning paradigms to model anxiety disorders in humans and animals have revealed contradictory results. While females exhibit the ability to rapidly acquire stimulus–response associations, which may result from a greater attentional bias towards threat, females are also capable to readily extinguish these associations. Thus, there is little evidence to suggest that the female sex represents a vulnerability factor of anxiety, per se. However, if females are to possess a second vulnerability factor that increases the inflexibility of stimulus–response associations, then an anxiety disorder may be more likely to develop. Behavioral inhibition (BI) is a vulnerability factor associated with the formation of inflexible stimulus–response associations. In this “two hit” model of anxiety vulnerability, females possessing a BI temperament will rapidly acquire stimulus–response associations that are resistant to extinction, resulting in the development of an anxiety disorder. In this review we explore evidence for a “two-hit” hypothesis underlying anxiety vulnerability in females. We explore the literature for evidence of a sex difference in attentional bias towards threat that may lead to the facilitated acquisition of stimulus–response associations in females. We also provide evidence that BI is associated with inflexible stimulus–response association formation. We conclude with data generated from our laboratory that highlights the additive effect of the female sex and behavioral inhibition vulnerabilities using a model behavior for anxiety disorder-susceptibility, active avoidance. © 2014

Allen M.T.,University of Northern Colorado | Allen M.T.,Stress and Motivated Behavior Institute | Myers C.E.,Neurobehavioral Research Laboratory | Myers C.E.,Rutgers University | And 3 more authors.
Behavioural Brain Research | Year: 2016

Recent work has found that behaviorally inhibited (BI) individuals exhibit enhanced eyeblink conditioning in omission and yoked training as well as with schedules of partial reinforcement. We hypothesized that spacing CS-US paired trials over a longer period of time by extending and varying the inter-trial interval (ITI) would facilitate learning. All participants completed the Adult Measure of Behavioural Inhibition (AMBI) and were grouped as behaviorally inhibited (BI) and non-behaviorally inhibited (NI) based on a median split score of 15.5. All participants received 3 US alone trials and 30CS-US paired trials for acquisition training and 20CS alone trials for extinction training in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS) and a 50-ms air puff unconditional stimulus (US). Participants were randomly assigned to receive a short ITI (mean = 30 +/- 5 s), a long ITI (mean = 57 +/- 5 s) or a variable long ITI (mean = 57 s, range 25-123 s). No significant ITI effects were observed for acquisition or extinction. Overall, anxiety vulnerable individuals exhibited enhanced conditioned eyeblink responses as compared to non-vulnerable individuals. This enhanced acquisition of CRs was significant in spaced training with a variable long ITI, but not the short or long ITI. There were no significant effects of ITI or BI on extinction. These findings are interpreted based on the idea that uncertainty plays a role in anxiety and can enhance associative learning in anxiety vulnerable individuals. © 2016 Elsevier B.V.

Roland J.J.,Rutgers University | Stewart A.L.,Rutgers University | Janke K.L.,Rutgers University | Gielow M.R.,Rutgers University | And 6 more authors.
Journal of Neuroscience | Year: 2014

The septohippocampal pathway contains cholinergic, GABAergic, and glutamatergic projections and has an established role in learning, memory, and hippocampal theta rhythm. Both GABAergic and cholinergic neurons in the medial septum-diagonal band of Broca (MSDB) have been associated with spatial memory, but the relationship between the two neuronal populations is not fully understood. The present study investigated the effect of selective GABAergic MSDB lesions on hippocampal acetylcholine (ACh) efflux and spatial memory during tasks that varied in memory demand. Male Sprague Dawley rats were given GABAergic lesions of the MSDB using GAT1-saporin (GAT1-SAP) and examined on spontaneous exploration (Experiment 1) and non-matching to position without (NMTP; Experiment 2) and with a delay (DNMTP; Experiment 3), while concurrently using in vivo microdialysis to measure hippocampal ACh efflux. Intraseptal GAT1-SAP treatment did not alter baseline or behaviorally stimulated hippocampal ACh efflux or maze exploration (Experiment 1). Moreover, GAT1-SAP did not alter evoked hippocampal ACh efflux related to NMTP nor did it impair working memory in NMTP (Experiment 2). In contrast, both ACh efflux and performance in DNMTP were impaired by intraseptal GAT1-SAP. Thus, GABAergic MSDB neurons are important for spatial working memory and modulate hippocampal ACh efflux under conditions of high memory load. The relationship between the septohippocampal cholinergic and GABAergic systems and working memory will be discussed. © 2014 the authors.

Holloway J.L.,Seton Hall University | Holloway J.L.,Stress and Motivated Behavior Institute | Beck K.D.,Stress and Motivated Behavior Institute | Beck K.D.,NeuroBehavioral Research Laboratory | And 2 more authors.
Behavioural Brain Research | Year: 2011

Sex differences in attentional processing and new motor learning remain controversial, and are complicated by the influence of endogenous and exogenous gonadal hormones. Facilitated acquisition of a classically conditioned eyeblink response in oral contraceptive-using women has been reported, as have menstrual cycle-dependent changes in pre-pulse inhibition (PPI). The current study sought to replicate and extend these findings by comparing acquisition of the conditioned eyeblink response and PPI in women currently taking oral contraceptives (OCs), women not taking OCs, as well as men. Women were assigned to participate either during their follicular or luteal menstrual cycle phase. Acquisition was assessed in a two-tone discrimination delay paradigm (500-ms conditional stimulus (CS); 100-ms airpuff unconditional stimulus (US)). PPI was lower in males and OC-users depending on stimulus intensity. Consistent with early classical conditioning research, females acquired an eyeblink conditioned response faster than males. Faster acquisition was associated with larger unconditional responses. Women taking OCs demonstrated accelerated conditioned response acquisition compared to women not taking OCs and males although unconditional responses were comparable to males. Facilitated acquisition of new motor learning in OC-users was replicated in a college-aged population of women and was not secondary to enhanced reactivity to sensory stimuli. © 2010.

Cominski T.P.,Rutgers University | Jiao X.,Veterans Affairs Biomedical Research Institute | Catuzzi J.E.,Rutgers University | Stewart A.L.,Veterans Affairs Biomedical Research Institute | And 2 more authors.
Frontiers in Behavioral Neuroscience | Year: 2014

The hippocampus has been implicated in anxiety disorders and post-traumatic stress disorder (PTSD); human studies suggest that a dysfunctional hippocampusmay be a vulnerability factor for the development of PTSD. In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders. First, the effect of hippocampal damage on avoidance learning was investigated in outbred Sprague Dawley (SD) rats. Second, the function of the hippocampus inWistar- Kyoto (WKY) rats was compared to SD rats. The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction. The results of the current study indicate that hippocampal damage in SD rats leads to impaired extinction of avoidance learning similar toWKY rats. Furthermore,WKY rats have reduced hippocampal volume and impaired hippocampal synaptic plasticity as compared to SD rats.These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD. © 2014 Cominski, Jiao, Catuzzi, Stewartand Pang.

Somlai Z.,Semmelweis University | Moustafa A.A.,Rutgers University | Keri S.,National Psychiatry Center | Keri S.,University of Szeged | And 3 more authors.
Schizophrenia Research | Year: 2011

Previous studies investigating feedback-driven reinforcement learning in patients with schizophrenia have provided mixed results. In this study, we explored the clinical predictors of reward and punishment learning using a probabilistic classification learning task. Patients with schizophrenia (n = 40) performed similarly to healthy controls (n = 30) on the classification learning task. However, more severe negative and general symptoms were associated with lower reward-learning performance, whereas poorer general psychosocial functioning was correlated with both lower reward- and punishment-learning performances. Multiple linear regression analyses indicated that general psychosocial functioning was the only significant predictor of reinforcement learning performance when education, antipsychotic dose, and positive, negative and general symptoms were included in the analysis. These results suggest a close relationship between reinforcement learning and general psychosocial functioning in schizophrenia. © 2010.

Myers C.E.,NeuroBehavioral Research Laboratory | Myers C.E.,Rutgers University | Bermudez-Hernandez K.,New York University | Bermudez-Hernandez K.,The Nathan Kline Institute for Psychiatric Research | And 2 more authors.
PLoS ONE | Year: 2013

Postnatal neurogenesis of granule cells (GCs) in the dentate gyrus (DG) produces GCs that normally migrate from the subgranular zone to the GC layer. However, GCs can mismigrate into the hilus, the opposite direction. Previous descriptions of these hilar ectopic GCs (hEGCs) suggest that they are rare unless there are severe seizures. However, it is not clear if severe seizures are required, and it also is unclear if severe seizures are responsible for the abnormalities of hEGCs, which include atypical dendrites and electrophysiological properties. Here we show that large numbers of hEGCs develop in a transgenic mouse without severe seizures. The mice have a deletion of BAX, which normally regulates apoptosis. Surprisingly, we show that hEGCs in the BAX-/- mouse have similar abnormalities as hEGCs that arise after severe seizures. We next asked if there are selective effects of hEGCs, i.e., whether a robust population of hEGCs would have any effect on the DG if they were induced without severe seizures. Indeed, this appears to be true, because it has been reported that BAX-/- mice have defects in a behavior that tests pattern separation, which depends on the DG. However, inferring functional effects of hEGCs is difficult in mice with a constitutive BAX deletion because there is decreased apoptosis in and outside the DG. Therefore, a computational model of the normal DG and hippocampal subfield CA3 was used. Adding a small population of hEGCs (5% of all GCs), with characteristics defined empirically, was sufficient to disrupt a simulation of pattern separation and completion. Modeling results also showed that effects of hEGCs were due primarily to "backprojections" of CA3 pyramidal cell axons to the hilus. The results suggest that hEGCs can develop for diverse reasons, do not depend on severe seizures, and a small population of hEGCs may impair DG-dependent function. © 2013 Myers et al.

Beck K.D.,Neurobehavioral Research Laboratory | Beck K.D.,Stress and Motivated Behavioral Institute | Jiao X.,Stress and Motivated Behavioral Institute | Pang K.C.H.,Neurobehavioral Research Laboratory | And 3 more authors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2010

The risk for developing anxiety disorders is greater in females and those individuals exhibiting a behaviorally inhibited temperament. Growth of behavioral avoidance in people is a significant predictor of symptom severity in anxiety disorders, including post-traumatic stress disorder. Using an animal model, our lab is examining how the process of learning avoidant behavior may lead certain individuals to develop anxiety. Here we examined whether the known vulnerabilities of female sex and behaviorally inhibited temperament have individual or additive effects upon the acquisition of an active-avoidance response. A discrete trial lever-press escape-avoidance protocol was used to examine the acquisition of behavioral avoidance in male and female Sprague-Dawley (SD) rats and behaviorally inhibited inbred Wistar-Kyoto (WKY) rats. Overall, WKY rats of both sexes were indistinguishable in their behavior during the acquisition of an active-avoidance response, exhibiting quicker acquisition of reinforced responses both between and within session compared to SD rats. Further WKY rats emitted more non-reinforced responses than SD rats. Sex differences were evident in SD rats in both the acquisition of the reinforced response and the emission of non-reinforced responses, with SD females acquiring the response quicker and emitting more non-reinforced responses following lever presses that led to an escape from shock. As vulnerability factors, behavioral inhibition and female sex were each associated with more prevalent reinforced and non-reinforced avoidant behavior, but an additive effect of these 2 factors was not observed. These data illustrate the importance of genetics (both strain and sex) in the assessment and modeling of anxiety vulnerability through the acquisition of active-avoidance responses and the persistence of emitting those responses in periods of non-reinforcement. © 2010.

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