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Preview: Behavioral Neuroscience - Vol 123, Iss 6

Behavioral Neuroscience - Vol 131, Iss 1

The primary mission of Behavioral Neuroscience is to publish original research papers in the broad field of the biological bases of behavior.

Last Build Date: Tue, 21 Feb 2017 03:00:35 EST

Copyright: Copyright 2017 American Psychological Association

Medial orbitofrontal cortex modulates associative learning between environmental cues and reward probability.


It has recently been recognized that orbitofrontal cortex has 2 subdivisions that are anatomically and functionally distinct. Most rodent research has focused on the lateral subdivision, leaving the medial subdivision (mOFC) relatively unexplored. We recently showed that inhibiting mOFC neurons eliminated the differential impact of reward probability cues on discrimination accuracy in a sustained attention task. In the present study, we tested whether increasing mOFC neuronal activity in rats would accelerate acquisition of reward contingencies. mOFC neuronal activity was increased using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) method, in which clozapine-N-oxide administration leads to neuronal modulation by acting on synthetic receptors not normally expressed in the rat brain. We predicted that rats with neuronal activation in mOFC would require fewer sessions than controls for acquisition of a task in which visual cues signal the probability of reward for correct discrimination performance. Contrary to this prediction, mOFC neuronal activation impaired task acquisition, suggesting mOFC may play a role in learning relationships between environmental cues and reward probability or for using that information in adaptive decision-making. In addition, disrupted mOFC activity may contribute to psychiatric conditions in which learning associations between environmental cues and reward probability is impaired. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Effects of endothelin-induced prefrontal cortical lesions on delay discounting in the rat.


Stroke is one of the most prominent causes of neurological disability, and the number of stroke cases worldwide is expected to grow due to increases in both average life span and population. As such, new methods for both acute treatment and poststroke rehabilitation will be increasingly necessary. Although a number of approaches to restoring motor function poststroke are in development, there are few methods to alleviate the cognitive deficits caused by this disease. As well, there are very few preclinical models of stroke with a specific focus on higher-order cognitive functions. The goal of the current experiments was to examine the effects of bilateral ischemic lesions, produced by targeted microinjections of endothelin-1 (ET-1) in the medial (mPFC) and orbital (oPFC) prefrontal cortices of adult male Sprague–Dawley rats (n = 39) on inhibitory control as measured through a delay discounting paradigm. The ET-1 injections to the mPFC and oPFC resulted in average lesion volumes of 17.98 mm3 ± 2.841 mm3 (Mean ± SE) and 26.05 mm3 ± 4.052 mm3 (Mean ± SE), respectively. During delay discounting testing, wherein animals were offered a small, immediately available food reward versus a large, but delayed reward, it was found that animals with lesions to the oPFC were more likely to choose the immediately available reward as compared to their mPFC or control counterparts. We conclude that using ET-1 in the oPFC may be a new and viable method to study the effects of ischemic lesions on higher-order cognitive dysfunction poststroke. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Successful and unsuccessful response inhibitions differentially affect the effective connectivity between insular, presupplementary-motor, and striatal areas.


Successful response inhibition depends upon the delay between the cues that signal a response and its subsequent inhibition. Previous studies report activity in the right presupplementary motor area (rPreSMA), right anterior insula (rAI), and the right striatum (rSTR) when subjects attempt to inhibit responses. Although these regions are anatomically connected, how they interact during successful and unsuccessful inhibitions has not been studied. In this work, we used a temporal prediction task, functional MRI, and dynamic causal modeling to solve this question. We found selective direct activation of both the rPreSMA and the rAI during successful and unsuccessful inhibitions which also were associated with opposite modulatory effects on insular-striatal and presupplementary-motor striatal descending connections. Moreover, inputs to the rPreSMA during successful inhibitions were propagated to the rAI whereas inputs to the rAI during unsuccessful inhibitions were propagated to the rPreSMA. We interpret that the direct perturbation in the rPreSMA and the modulation of the rPreSMA → rSTR connections would facilitate response inhibition whereas weak insular activity would cause response inhibition to fail despite the existence of strong rAI → rSTR modulations. We discuss that descending connections could be nonlinearly modulated via activity of either the right inferior frontal gyrus or the left anterior cingulate cortex. From a predictive coding perspective, rAI activity during successful and unsuccessful inhibition would signal interoceptive information when subjects unexpectedly need to change behaviors. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Phosphorylation of tyrosine receptor kinase B in the dorsal striatum and dorsal hippocampus is associated with response learning in a water plus maze.


The dorsal hippocampus and dorsal striatum have dissociable roles in learning and memory that are related to region-specific changes in proteins necessary for neuronal plasticity and memory formation. There is additional evidence that the hippocampus and striatum can interact during memory formation. Phosphorylation of tyrosine receptor kinase B is important for memory formation in the hippocampus, but whether or not it has a role in striatum-dependent learning, or in interactions between the hippocampus and striatum, has not been examined. In the present study, we tested the hypothesis that response training increases pTrkB in the dorsal striatum, but decreases pTrkB in dorsal hippocampus, due to an interaction between the systems during memory formation. Results show a significant decrease in pTrkB levels in the dorsal hippocampus of rats trained on the response task compared with swim controls. Response training did not increase pTrkB levels in the dorsal striatum. Positive correlations were found between response learning and the total area of cells expressing pTrkB in the dorsal striatum, while no correlations were found in swim controls. Our results partially support our hypothesis and indicate that response learning is associated with a decrease in hippocampal pTrkB, while phosphorylation of TrkB in the dorsal striatum remains constant. This indicates that suppression of hippocampal pTrkB during response learning may be involved in striatum-dependent memory formation. Additionally, our findings suggest that activation of TrkB in a sparse arrangement of cells may be associated with faster acquisition of a response task. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

The ventral dentate gyrus mediates pattern separation for reward value.


Rats with ventral dentate gyrus (DG) lesions, sham lesions, and controls were run in a runway for 20 pellets of food. After reaching running speed asymptote, the number of pellets was reduced to 1, 9, or 17 pellets. The purpose of the present experiment was to determine whether the ventral DG subregion of the hippocampus plays a role in pattern separation for reward value. The results indicated that sham lesioned and control rats displayed a graded decrease in runway velocities, supporting a pattern separation process. In contrast, ventral DG lesioned rats continued to maintain runway velocities regardless of the reward-value shifts. The ventral DG lesion results do not appear to be due to hyperactivity but could be based on the idea that the ventral DG is part of a decision-making circuitry to predict goal-relevant reward outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Retrograde amnesia of contextual fear conditioning: Evidence for retrosplenial cortex involvement in configural processing.


It has been suggested that contextual fear conditioning can be supported by either an elemental system, where individual features of the environment are associated with shock, or a configural system, where environmental features are bound together and associated with shock. Although the retrosplenial cortex (RSC) is known to be involved in contextual fear conditioning, it is not clear whether it contributes to the elemental or configural system. To isolate the role of the RSC in contextual fear conditioning, the current experiments examined the influence of RSC lesions on the context preexposure facilitation effect, a procedure known to produce conditioning to a configural representation of context. In Experiment 1, rats that were preexposed to the conditioning context froze more compared to rats that were not, replicating the context preexposure facilitation effect. Although pretraining lesions of the RSC had no impact on the context preexposure facilitation effect (Experiment 2a), posttraining lesions attenuated the effect (Experiment 2b), suggesting that the RSC normally contributes to a configural context representation. Retrohippocampal contributions to contextual fear conditioning are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Age-related impairment on a forced-choice version of the Mnemonic Similarity Task.


Previous studies from our lab have indicated that healthy older adults are impaired in their ability to mnemonically discriminate between previously viewed objects and similar lure objects in the Mnemonic Similarity Task (MST). These studies have used either old/similar/new or old/new test formats. The forced-choice test format (e.g., “Did you see object A or object A′ during the encoding phase?”) relies on different assumptions than the old/new test format (e.g., “Did you see this object during the encoding phase?”); hence, converging evidence from these approaches would bolster the conclusion that healthy aging is accompanied by impaired performance on the MST. Consistent with our hypothesis, healthy older adults exhibited impaired performance on a forced-choice test format that required discriminating between a target and a similar lure. We also tested the hypothesis that age-related impairments on the MST could be modeled within a global matching computational framework. We found that decreasing the probability of successful feature encoding in the models caused changes that were similar to the empirical data in healthy older adults. Collectively, our behavioral results using the forced-choice format extend the finding that healthy aging is accompanied by an impaired ability to discriminate between targets and similar lures, and our modeling results suggest that a diminished probability of encoding stimulus features is a candidate mechanism for memory changes in healthy aging. We also discuss the ability of global matching models to account for findings in other studies that have used variants on mnemonic similarity tasks. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Early amygdala or hippocampus damage influences adolescent female social behavior during group formation.


This study continues a longitudinal analysis of rhesus macaque social behavior following bilateral neonatal ibotenic acid lesions of the amygdala or hippocampus, or sham operations. The social behavior of female subjects was evaluated at a critical developmental time point—the transition to adulthood. At approximately 4 years of age, female subjects were housed in small groups with other female subjects and reproductively viable adult males. As compared with neurologically intact control animals and animals with early amygdala damage, animals with early hippocampal damage were more social with their female peers. In contrast, as compared with control animals, animals with early amygdala damage spent less time with the males, engaged less frequently in behaviors typical of reproductive consortships, had higher frequencies of self-directed stereotypies, and became pregnant later. Males also generated fewer communicative signals toward animals with early amygdala damage than to control animals and animals with early hippocampus damage. Rates of sexual behavior were generally low for all animals, and there were no lesion-based differences in their frequencies. Discriminant function analyses demonstrated that patterns of affiliative social behaviors differed across the 3 experimental groups, both in terms of the social behaviors directed to the males, and the social behaviors generated by the males toward the females. In 4 of the 5 social groups, amygdala-lesioned animals were lowest ranked, potentially contributing to reduced sociability interactions with males. Other potential mechanisms and the experiments needed to elucidate them are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Intervention with the mother–infant relationship reduces cell proliferation in the Locus Coeruleus of female rat pups.


The Locus Coeruleus (LC) is a noradrenergic nucleus involved in several neuroendocrine and behavioral functions. During the neonatal period, the LC is critical for olfactory learning. Full development occurs during the early postnatal period. Environmental interventions after birth may affect neurogenesis. In rats, the neonatal handling procedure has been used as a model to analyze the effects of environmental intervention early in life. It has been related to several long-lasting behavioral and neuroendocrine changes. The present study analyzed the effects of handling on the number of neurons, cellular proliferation, and apoptosis in the LC of 11-day-old female rats. Wistar rat pups were submitted to brief maternal separation followed by handling (1 min per day from postnatal day [PND] 1 to 10). On PND 11, the LC was analyzed using immunohistochemistry for NeuN and BrdU, TUNEL staining, and electron microscopy. The intervention reduced the number of neurons in the LC but showed no significant change in the number of apoptotic cells, as measured by the TUNEL technique. However, the number of proliferating cells was significantly lower in the handled rat pups as compared with the nonhandled ones. This study demonstrates that the infant LC is sensitive to changes in maternal behavior. A seemingly mild environmental intervention during the neonatal period may reprogram the development of the LC, altering cell proliferation. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Stimulation of 5-HT2A receptors recovers sensory responsiveness in acute spinal neonatal rats.


Quipazine is a 5-HT2A-receptor agonist that has been used to induce motor activity and promote recovery of function after spinal cord injury in neonatal and adult rodents. Sensory stimulation also activates sensory and motor circuits and promotes recovery after spinal cord injury. In rats, tail pinching is an effective and robust method of sacrocaudal sensory afferent stimulation that induces motor activity, including alternating stepping. In this study, responsiveness to a tail pinch following treatment with quipazine (or saline vehicle control) was examined in spinal cord transected (at midthoracic level) and intact neonatal rats. Rat pups were secured in the supine posture with limbs unrestricted. Quipazine or saline was administered intraperitoneally and after a 10-min period, a tail pinch was administered. A 1-min baseline period prior to tail-pinch administration and a 1-min response period postpinch was observed and hind-limb motor activity, including locomotor-like stepping behavior, was recorded and analyzed. Neonatal rats showed an immediate and robust response to sensory stimulation induced by the tail pinch. Quipazine recovered hind-limb movement and step frequency in spinal rats back to intact levels, suggesting a synergistic, additive effect of 5-HT-receptor and sensory stimulation in spinal rats. Although levels of activity in spinal rats were restored with quipazine, movement quality (high vs. low amplitude) was only partially restored. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Cognitive impairment in heart failure: A protective role for angiotensin-(1-7).


Patients with congestive heart failure (CHF) have increased hospital readmission rates and mortality if they are concomitantly diagnosed with cognitive decline and memory loss. Accordingly, we developed a preclinical model of CHF-induced cognitive impairment with the goal of developing novel protective therapies against CHF related cognitive decline. CHF was induced by ligation of the left coronary artery to instigate a myocardial infarction (MI). By 4- and 8-weeks post-MI, CHF mice had approximately a 50% and 70% decline in ejection fraction as measured by echocardiography. At both 4- and 8-weeks post-MI, spatial memory performance in CHF mice as tested using the Morris water task was significantly impaired as compared with sham. In addition, CHF mice had significantly worse performance on object recognition when compared with shams as measured by discrimination ratios during the novel object recognition NOR task. At 8-weeks post-MI, a subgroup of CHF mice were given Angiotensin (Ang)-(1–7) (50mcg/kg/hr) subcutaneously for 4 weeks. Following 3 weeks treatment with systemic Ang-(1–7), the CHF mice NOR discrimination ratios were similar to shams and significantly better than the performance of CHF mice treated with saline. Ang-(1–7) also improved spatial memory in CHF mice as compared with shams. Ang-(1–7) had no effect on cardiac function. Inflammatory biomarker studies from plasma revealed a pattern of neuroprotection that may underlie the observed improvements in cognition. These results demonstrate a preclinical mouse model of CHF that exhibits both spatial memory and object recognition dysfunction. Furthermore, this CHF-induced cognitive impairment is attenuated by treatment with systemic Ang-(1–7). (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)

Differential patterns of constant frequency 50 and 22 khz usv production are related to intensity of negative affective state.


Adult rat ultrasonic vocalizations (USVs) are a valuable tool for noninvasively assessing an animal’s emotional state. USVs are produced in 1 of 2 frequency ranges labeled as 22 kHz or 50 kHz vocalizations. One USV subtype within the 50 kHz call category, constant frequency 50 kHz (CF 50 kHz) calls, is not viewed as signaling an emotional state. The current study tested the hypothesis that CF 50 kHz calls are related to a mild negative affective state. In Experiment 1, diazepam (1, 2.5, or 5 mg/kg), or control injections were administered prior to receiving a sequence of mild footshocks (0.5 mA, 0.5 s). Subjects transitioned from producing CF 50 to 22 kHz USVs as footshocks were repeated; a pattern paralleled by a shift from rearing to increased time freezing. USV production was largely absent in the higher diazepam dose groups, whereas the 1 mg/kg dose attenuated CF 50 kHz USV production prior to and immediately following initial footshocks. The higher doses of diazepam similarly reduced rearing activity and overall freezing behavior. In Experiment 2, pre-exposure to the testing environment with or without access to palatable food elicited CF 50 kHz calls and rearing. During re-exposure to the test chamber the following day, CF 50 kHz USV production was reduced prior to footshock onset compared to the prior test day. The pattern of results support an association between CF 50 kHz USVs and a mild negative affective state; dissociating this call type may increase the sensitivity of behavioral measurements of emotion. (PsycINFO Database Record (c) 2017 APA, all rights reserved)(image)