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Preview: Behavioral Neuroscience - Vol 123, Iss 6

Behavioral Neuroscience - Vol 130, Iss 6

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: Mon, 23 Jan 2017 12:00:35 EST

Copyright: Copyright 2017 American Psychological Association

Introduction to the special section on new ideas about cerebellar function.


Richard Thompson’s seminal contributions to neuroscience include the discovery of the cerebellar interpositus nucleus as the site of essential plasticity in the formation of the conditioned eyeblink response. In this section, context for this body of research is provided, as well as new findings on cerebellar function using a range of procedures. Current work on the role of the cerebellum in learning and memory include studies of the cellular and molecular mechanisms of plasticity in cortex and deep nuclei, as well as functional magnetic resonance imaging studies in humans. Together, these papers provide a glimpse into new directions in the study of cerebellum and cognition. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

The search for the engram in eyeblink conditioning: A synopsis of past and present perspectives on the role of the cerebellum.


One of the most prolific behavioral neuroscientists of his generation, Richard F. Thompson published more than 450 research articles during his almost 60-year career before his death in 2014. The breadth and reach of his scholarship has extended to a large multidisciplinary audience of scientists. The focal point of this article is arguably his most influential paper on cerebellar classical conditioning entitled “The Neurobiology of Learning and Memory” that appeared in Science in 1986 and has been cited 700 times since its publication. Here, a summary of the initial Thompson laboratory research leading up to an understanding of the cerebellum and its critical role in memory traces will be discussed, along with conclusions from the Science article pertinent to cerebellar classical conditioning. The summary will also discuss how the original 1986 article continues to stimulate and influence new research and provide further insights into the role of the cerebellum in the neurobiology of learning and memory function relevant to studies of mammalian classical conditioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Systematic variation of acquisition rate in delay eyelid conditioning.


Averaging artifacts inherent in group acquisition curves can mask behavioral phenomena that are potentially revealing in terms of underlying neural mechanisms. To address this, we implemented a behavioral analysis of 106 rabbits trained over 4 sessions using delay eyelid conditioning. Group results showed the typical monotonic increase in conditioned responses (CRs). For most subjects CRs first appeared (as indexed by the criterion of 8 CRs in 9 trials) during the first 18 trials of the second training session. Subdividing subjects according to the training block at which they met criterion revealed systematic differences in the subsequent rate that CR amplitudes increased, but not in asymptotic CR amplitudes. Subjects meeting criterion early in sessions showed more rapid increases in CR amplitude than those meeting criterion later in sessions. This effect was solely dependent on how early within a session criterion was met, as subjects meeting criterion at the beginning of the third and fourth sessions showed more rapid increases in CR amplitude than those meeting criterion after the first 18 trials of the second session. The exceptions were the 7% of the subjects that met criterion late in the first session. Their CR amplitudes increased at a rate similar to subjects meeting criterion early in sessions. These results suggest an interplay between consolidation processes and a previously reported short-term plasticity process that makes CR acquisition a nonmonotonic and complex function of the point during training sessions at which CRs first appear. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Intracerebellar infusion of the protein kinase M zeta (PKMζ) inhibitor zeta-inhibitory peptide (ZIP) disrupts eyeblink classical conditioning.


Protein kinase M zeta (PKM-ζ), a constitutively active N-terminal truncated form of PKC-ζ, has long been implicated in a cellular correlate of learning, long-term potentiation (LTP). Inhibition of PKM-ζ with zeta-inhibitory peptide (ZIP) has been shown in many brain structures to disrupt maintenance of AMPA receptors, irreversibly disrupting numerous forms of learning and memory that have been maintained for weeks. Delay eyeblink conditioning (EBC) is an established model for the assessment of cerebellar learning; here, we show that PKC-ζ and PKM-ζ are highly expressed in the cerebellar cortex, with highest expression found in Purkinje cell (PC) nuclei. Despite being highly expressed in the cerebellar cortex, no studies have examined how regulation of cerebellar PKM-ζ may affect cerebellar-dependent learning and memory. Given its disruption of learning in other brain structures, we hypothesized that ZIP would also disrupt delay EBC. We have shown that infusion of ZIP into the lobulus simplex of the rat cerebellar cortex can indeed significantly disrupt delay EBC. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Cerebellar activation during motor sequence learning is associated with subsequent transfer to new sequences.


Effective learning results not only in improved performance on a practiced task, but also in the ability to transfer the acquired knowledge to novel, similar tasks. Using a modified serial reaction time (RT) task, the authors examined the ability to transfer to novel sequences after practicing sequences in a repetitive order versus a nonrepeating interleaved order. Interleaved practice resulted in better performance on new sequences than repetitive practice. In a second study, participants practiced interleaved sequences in a functional MRI (fMRI) scanner and received a transfer test of novel sequences. Transfer ability was positively correlated with cerebellar blood oxygen level dependent activity during practice, indicating that greater cerebellar engagement during training resulted in better subsequent transfer performance. Interleaved practice may thus result in a more generalized representation that is robust to interference, and the degree of activation in the cerebellum may be a reflection of the instantiation and engagement of internal models. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Cerebellar response to familiar and novel stimuli: An fMRI study.


Historically known for its key contribution to motor behavior, the cerebellum continues to break boundaries. Researchers have demonstrated the cerebellum also plays a role in learning, memory, and more recent evidence for contributions in language, attention, working memory, emotions, and social processes. Here, we present a study that adds to the list of nonmotor processes of the cerebellum. We used images of faces and outdoor scenes to examine the cerebellar response to familiar and novel stimuli. Participants were familiarized with a subset of stimuli, and then underwent functional MRI (fMRI) where they were presented with the previously stimuli and new stimuli while making “old” and “new” judgment. In a familiar versus novel contrast, familiar stimuli (faces and scenes combined) activated bilateral regions of the cerebellum including I–IV, V, VI, Crus I, and Crus II. When separated by type, familiar faces had greater activation of bilateral I–IV than novel faces. These results demonstrate the cerebellar role in determining familiarity and contribute to continuing research supporting cerebellar contributions to nonmotor processes. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Ventral striatal lesions disrupt dopamine neuron signaling of differences in cue value caused by changes in reward timing but not number.


We recently showed that ventral striatal (VS) lesions abolished reward prediction errors that reflect changes in reward timing while leaving relatively unaffected errors that reflect changes in reward number. Here we extended those results by examining whether normal learning-related changes in firing to the reward-predictive cues in the same dopamine neurons were also disrupted by VS lesions. This analysis revealed that dopamine neurons recorded in VS-lesioned rats failed to show value-related changes in firing to the cues in timing but showed normal changes in number blocks. This effect suggests that the loss of reward-evoked error signals in the timing blocks impaired encoding of the cue value in downstream areas, which then supply these predictions to dopamine neurons at the time of cue presentation. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Serotonin, estrus, and social context influence c-Fos immunoreactivity in the inferior colliculus.


A fundamental task of sensory systems is to extract relevant social information from a range of environmental stimuli in the face of changing behavioral contexts and reproductive states. Neuromodulatory pathways that interact with such contextual variables are 1 mechanism for achieving this. In the mouse inferior colliculus (IC), a midbrain auditory region, the neuromodulator serotonin increases in females interacting with courting males, but events downstream of serotonin release have not been investigated. Here, we manipulated serotonin levels in female mice with the serotonin releaser fenfluramine or the serotonin depleter para-chlorophenylalaninemethyl ester (pCPA). Females were then exposed to an empty cage, a male partner, or a playback of courtship vocalizations, and the numbers of neurons in the IC with positive immunoreactivity for the immediate early gene product c-Fos were measured. The effects of drug treatments depended on social context and estrous state. Fenfluramine had greater effects in the nonsocial than in the partner social treatments. Females in proestrus or estrus and given fenfluramine had higher densities of c-Fos immunoreactive neurons, while females in diestrus had fewer immunoreactive neurons. The drug pCPA had the expected opposite effect of fenfluramine, causing a decreased response in pro/estrus females and an increased response in diestrus females. These findings show that the effects of serotonin on c-Fos activity in the IC of females is dependent on both external context and reproductive state, and suggest that these effects occur downstream of serotonin release. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Estradiol is associated with altered cognitive and physiological responses during fear conditioning and extinction in healthy and spider phobic women.


The first-line psychological treatment for anxiety disorders is exposure therapy, which can be modeled in the laboratory using fear extinction. In healthy women, estradiol levels predict return of fear following extinction, whereas low levels are associated with greater return of fear. Investigating whether estradiol is similarly associated with extinction in clinically anxious women may provide insight to mechanisms underlying symptom relapse following exposure therapy. In the present study, women with spider phobia and healthy women participated in a 2-day fear conditioning and extinction procedure during a period of high or low estradiol levels. Skin conductance responses, shock expectancy, and valence ratings were measured throughout. Women exhibited comparable decreases in physiological arousal from conditioning to the end of extinction training on Day 1. However, compared to women with high estradiol, and irrespective of clinical status, women with low estradiol exhibited significant return of physiological arousal at extinction recall on Day 2, despite accurate ratings regarding the likelihood of shock. Low estradiol women also reported heightened threat expectancy and physiological responding during presentation of safety cues. These results may point to novel means of enhancing exposure therapy in women by timing treatment delivery during periods of higher estradiol levels. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Participation of progesterone receptors in facilitation and sequential inhibition of lordosis response induced by ring A-reduced progesterone metabolites in female mice.


Sexual receptivity in female rodents induced by the sequential injection of estrogen and progesterone is followed by a period in which females do not respond behaviorally to a second administration of progesterone (P); this is known as sequential inhibition. It has been proposed that the induction of sequential inhibition by progesterone in rats depends on down regulation of the progesterone receptor (PR) in brain areas involved in the expression of female sexual receptivity. P is rapidly metabolized to a variety of 5α- or 5β-ring A-reduced progestins (RPrg). These RPrg have little or no affinity for the PR. They stimulate sexual receptivity (lordosis) more potently than P itself in estrogen-primed rats and do not induce sequential inhibition. The purpose of the current study was to test the role of the PR in the facilitation of lordosis and sequential inhibition induced by P and the following RPrg: 5α-pregnandione (5α-DHP), 5α,3β-pregnanolone (5α,3β-Pgl), 5β-pregnanedione (5β-DHP), and 5β,3α-pregnanolone (5β,3α-Pgl) in ovariectomized (ovx) female mice primed with estradiol benzoate. The RPrg were tested in C57BL/6 mice and in a strain lacking the progesterone receptor expression (PRKO). Our results show that both facilitation and sequential inhibition of lordosis induced by progesterone require the presence of the progesterone receptor. Interestingly, some RPrg facilitate lordosis but do not induce sequential inhibition in female mice. Sexual receptivity induced by RPrg does not require the progesterone receptor. Thus, RPrg induce sexual receptivity, but they probably exert their effects through a different cellular mechanism that does not involve the progesterone receptor. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)

Effects of hydrocortisone on false memory recognition in healthy men and women.


Most of the studies focusing on the effect of stress on false memories by using psychosocial and physiological stressors yielded diverse results. In the present study, we systematically tested the effect of exogenous hydrocortisone using a false memory paradigm. In this placebo-controlled study, 37 healthy men and 38 healthy women (mean age 24.59 years) received either 10 mg of hydrocortisone or placebo 75 min before using the false memory, that is, Deese-Roediger-McDermott (DRM), paradigm. We used emotionally charged and neutral DRM-based word lists to look for false recognition rates in comparison to true recognition rates. Overall, we expected an increase in false memory after hydrocortisone compared to placebo. No differences between the cortisol and the placebo group were revealed for false and for true recognition performance. In general, false recognition rates were lower compared to true recognition rates. Furthermore, we found a valence effect (neutral, positive, negative, disgust word stimuli), indicating higher rates of true and false recognition for emotional compared to neutral words. We further found an interaction effect between sex and recognition. Post hoc t tests showed that for true recognition women showed a significantly better memory performance than men, independent of treatment. This study does not support the hypothesis that cortisol decreases the ability to distinguish between old versus novel words in young healthy individuals. However, sex and emotional valence of word stimuli appear to be important moderators. (PsycINFO Database Record (c) 2016 APA, all rights reserved)(image)