Jaak Panksepp Festschrift in May of 2010
The J.P. Scott Neuroscience Center hosted a FESTSCHRIFT for Dr. Jaak Panksepp on May 21-22 of 2010.
It was a terrific success!
Thanks to all the participants for coming and sharing their experiences and research over the two day event.
SYMPOSIUM for Dr. Panksepp on Saturday May 22nd Speakers
Modeling social affect in young mice
This talk will survey our laboratory’s work using adolescent mice to study the motivational and affective states that underpin genetically based differences in social behavior. We have identified stable, strain-dependent influences on social approach behavior, socially induced vocalizations, social reward and emotional responsiveness to conspecific distress. More recent studies have begun to identify some of the genetic and neurobiological substrates underlying these phenotypes. Our lab’s experimental approach has been uniquely fertilized by Panksepp’s unparalleled empirical and theoretical contributions to understanding the biological and evolutionary foundations of emotions
In 1988, I began my research on motivation in the laboratory of Jaak Panksepp. For my master’s thesis, I studied effects of early maternal separation on social motivation as reflected by juvenile play in rats. My motivation research changed its course when I heard Jaak say “reward is exploration”. This insightful notion led me to study brain stimulation reward-induced sniffing in rats for my prelim and guided my PhD dissertation and subsequently postdoctoral work. My talk will summarize my recent research on the neurobiology of reward.
Howard Casey Cromwell
The study of attachment motivation using maternal odor conditioning
In his typical pioneering spirit, Jaak Panksepp designed and used a novel maternal odor place preference conditioning task with rat pups. In Nelson and Panksepp (1996), it was used to show oxytocin is crucial for normal expression of bonding between caregiver and care-seeker. The ideas and results were prescient to the current focus on oxytocin as ‘the bonding hormone’. We have used the same measure to examine three different animal models of emotional impairment in early development. One model has used prenatal stress to alter early hormonal and neural systems. A second model has used perinatal exposure to polychlorinated biphenyls (PCBs) as an early stressor. The third model takes advantage of a selective breeding line of animals to examine pups from dams that emit higher or lower levels of 50 kHz ultrasounds. In each model, we have found significant alteration in early behavioral systems involved in attachment. Prenatal stress leads to a generalized preference for the odor cue merely based on familiarity and not maternal care while the toxin exposure dramatically reduces odor preference. The selective breeding line animals diverge as expected and the most prominent finding is a loss of cue preference in the low-line condition. Comparing these similarities and differences between the models has helped us develop our ideas about environmental and genetic interactions that influence essential dynamics between the care-giver and care-seeker in forming social bonds.
Play, distress and the filial bond in a social rodent , Octodon degus
In recent years Octodon degus, a biparental rodent with precocious young, has become an increasingly popular animal model for early childhood separation and associated depression-like brain changes. The behavior of degus is characterized by complex social interactions, which are frequently likened to that of humans and other primates. There is now abundant evidence for a host of neurophysiological changes taking place in response to social manipulations during early infancy, yet the behavioral consequences of the observed morphological and neurochemical alterations are poorly understood. In part this gap between brain and behavior is rooted in our lack of knowledge on the behavior and social interactions of this species; only little is known of the nature of the social bond between adult degus and their offspring. The developmental time course of behaviors found during infancy and adolescence including vocalizations, the separation response and play need to be studied in much more detail before we can start to use this promising animal model to its full potential. Here I will present a summary of the behavioral work conducted at Washington State University in an attempt to begin to address some of these questions.
Uncovering the molecular basis of positive affect using rough-and-tumble play in rats: A role for Insulin-Like Growth Factor 1
Positive emotional states have been shown to confer resilience to depression and anxiety in humans, but the molecular mechanisms underlying these effects have not yet been elucidated. In laboratory rats, positive emotional states can be measured by 50-kHz ultrasonic vocalizations (hedonic USVs), which are maximally elicited by juvenile rough-and-tumble play behavior. Using a focused microarray platform, insulin-like growth factor I (IGFI) extracellular signaling genes were found to be upregulated by hedonic rough-and-tumble play but not depressogenic social defeat. Administration of IGFI into the lateral ventricle increased rates of hedonic USVs in an IGFI receptor (IGFIR)-dependent manner. Lateral ventricle infusions of a siRNA specific to the IGFIR decreased rates of hedonic 50-kHz USVs. These results show that IGFI plays a functional role in the generation of positive affective states and that IGFI-dependent signaling is a potential therapeutic target for the treatment of depression and anxiety.
Biological mechanisms of drug-sensitive reward: lessons from an invertebrate model system
Affective communication: Pleasure seeking and birdsong
Appropriate vocal communication is at the heart of successful social interactions in a range of animal species, including humans. In some species, such as songbirds, brain mechanisms underlying vocal production have been well-defined, however little is known about the neural basis of the motivation to communicate or how the brain ensures that communication occurs within a socially appropriate context. Songbirds produce high rates of song within multiple social contexts, suggesting that they are highly motivated to sing and that the act of singing itself may be rewarding. Songbirds also adjust song so that it is appropriate within a given social context. Across vertebrate species, the neurotransmitter dopamine and opioid neuropeptides regulate motivation and reward, respectively. In songbirds, dopamine, opioids, and their receptors are found throughout the song control system and within several brain regions implicated in both motivation and reward. Growing research shows these regions to play a role in birdsong that differs depending upon whether song is sexually-motivated in response to a female, used for territorial defense or sung as part of a flock but not directed towards an individual (undirected song). Behavioral tests, pharmacological manipulations, and immunocytochemical data support the hypothesis that dopamine activity underlies the motivation or drive to sing, but that opioid release is what makes song production rewarding.
Inflammatory signaling pathways at the interface between stress physiology, endocrine function and behavior
Accumulating evidence suggests that exposure to psychological stressors leads to increased expression of pro-inflammatory cytokines and activation of inflammatory-related pathways in the central nervous system. Several logical predictions arise from these findings: (1) stressor exposure should produce changes in behavior that are reminiscent of acute illness; (2) administration of anti-inflammatory agents should ameliorate some behavioral consequences of stressor exposure; and (3) there should be convergence between anatomical and neurochemical pathways activated by stressor exposure and those involved in mitigating sickness behaviors. Importantly, these predictions have been tested in our laboratory across multiple stressor paradigms (footshock, maternal separation, and during acute alcohol withdrawal) using two species (rats and guinea pigs), suggesting that sickness may represent a more general motivational state that can be elicited by a diverse range of psychological challenges. Implications of these findings for understanding stress-related changes in behavior, mood and neuroinflammatory processes will be discussed.
The antidepressant and anxiolytic properties of GLYX-13: a novel NMDA receptor glycine site functional partial agonist
The N-methyl-D-aspartate receptors (NMDAR) play a central role in modulating normal synaptic transmission, synaptic plasticity, and excitotoxicity in the central nervous system. Recent human clinical studies with known NMDAR antagonists CP-101,606 and ketamine have found significant reductions in depression scores in patients with treatment-resistant depression. GLYX-13 is a tetrapeptide (TPPT) and is a glycine site functional partial agonist (GFPA) of the NMDAR. GLYX-13 has shown several aspects of novel pharmacology at NMDARs, and also does not display the classic side effects of known NMDAR modulators. In vitro studies have shown that GLYX-13 can markedly elevate long-term potentiation (LTP) while simultaneously reducing long-term depression (LTD) in rat hippocampal organotypic cultures-a property unique among NMDAR modulators. Moreover, GLYX-13 acts predominantly at NR2B-containing NMDARs. GLYX-13 is an effective neuroprotectant in both hippocampal slice cultures subjected to oxygen-glucose deprivation and in a gerbil model of hypoxia. GLYX-13 displayed significant antidepressant-like and anxiolytic-like properties in rats tested in the forced swim (Porsolt) and open field tests, respectively. In contrast to SSRIs, GLYX-13’s onset of action was within minutes of a single dose, affected both the positive and negative symptoms of depression, and induced resilience to depression as well. Thus, GLYX-13 is an attractive candidate for the treatment of depression.
MUSIC AS A NON-PHARMACOLOGICAL INTERVENTION IN CLINICAL PAIN PATIENTS
BACKGROUND: Pain is still a problem in most patients. Whereas the efficacy of pharmacological treatment with systemic and regional analgesia techniques is well proved, the efficacy of music as a non pharmacological intervention for the treatment of pain has not been established well enough: Music has been found to affect and stimulate brain and body in every-day life including various beneficial health consequences. It has an amazing power to stimulate many social-emotional processes. This emotional power is used as a non-pharmacological intervention in pain patients: It alleviates pain, stress and feelings of depression and some cognitions such as helplessness and hopelessness in patients suffering from acute and chronic pain.
AIM: The aim of this presentation is to evaluate the effect of music on acute and chronic pain and to present a strategy of a non-pharmacological interdisciplinary pain therapy module with music.
MAIN CONTRIBUTION: Many studies have shown big benefits with music listening for pain patients. Music played to premature babies may help to reduce their pain and encourage better oral feeding. Other outcomes most often reported were reduction of heart rate, respiratory rate and oxygen saturation. 51 studies including 3663 subjects, summarised up by a Cochrane report (Cepeda MS, Carr DB, Lau J, Alvarez H, 2006) have shown that listening to music reduces pain intensity levels by more than 50 % and it reduced opioid requirements. Subjects exposed to music had a 70 % greater probability of having at least 50 % of pain relief than unexposed subjects. This is equivalent to a NNT of 5. These studies included people with pain during a diagnostic or therapeutic procedure such as colonoscopy, lithotripsy, with postoperative pain as well as chronic non-cancer pain, cancer pain, labor pain or experimental pain.
IMPLICATIONS: The successful treatment of acute and chronic pain remains to be very important. The implementation of the multimodal pain therapy including non-pharmacological interventions with music still lacks in many therapeutical regimens. Music should not be used as a first line treatment for pain relief, but it could enhance therapy effectiveness and should be used as a non-pharmacological intervention in combination to other common treatment forms. It is now necessary to get more research done in order to establish guidelines for using music in modern multimodal therapy strategies.
ACKNOWLEDGEMENTS: This paper is dedicated to Jaak Panksepp. The financial support of the University of Salzburg, Austrian Pain Society and the Sokrates Stiftung (Schweiz) is acknowledged.
Sounds of Emotion and Synchronization of Frontal Theta Rhythms
The human brain is constantly assessing a multitude of sights and sounds to determine their relative significance and the urgency with which the person should respond. The affective component of these stimuli allows a person to instinctively identify safe versus threatening situations. While these emotional responses are generated from deep in the brain's circuitries, corresponding changes emerge in the activity of the brain's higher, cortical regions. Attempts to identify typical versus atypical emotional responding in the brain often suffer from difficulties monitoring rapid changes in the lower brain. In contrast, a real-time assessment of corresponding changes can be monitored in the electrical rhythms generated from cortical regions and measured with an electroencephalogram. In the current research, responses to short bursts of auditory representations of emotion were presented to participants while data were collected from a 19-electrode array on their scalps. The data were analyzed using the event-related synchronization algorithm to assess brain activity changes concurrent with short sounds of joy, pleasure, anger and sadness. Overall, the most apparent changes that differentiated between emotion types were found in the theta rhythm (3.5-7.5Hz). Specifically, women demonstrated increased theta in response to sounds of anger, while men showed elevated theta during sounds of pleasure. Further analyses suggest the gender difference was not due to change in an overall affective state, but rather are more likely to be indicative of initial appraisal processes related to the communication of emotion. Evaluating affective responses using the ERS algorithm appears to be one appropriate method for measuring immediate and transient neural changes related to emotion, and may be one tool for evaluating typical versus atypical affective response patterns in women and men
Have you seen the actors outside?
We experience the world by observing our own body changes responding tothe environment. This basic experience is a self-creating process, the associatedmotory tendencies subserving survival values. Action seems to play a keyrole in providing ‘meaning’ for these primary sensations. I suggest that it is a kind of action that can lead to an on-going maintenance of sensory invariance. In my view, the conscious states of ‘feelings’ that Jaak Panksepp has originally and so convincingly opened for scientific investigations, are emerging from these sensory invariant principles. In accord with this view, a number of very recent studies also suggest that it needs reproducible neuronal response patterns to sensory stimuli to gain ‘meaning’ or consciousness of sensory states (e.g. Schwarzkopf & Rees, Science, 327, 2010). I will demonstrate some of these aspects by the chicken model that I have learned from Jaak about 30 years ago. The behaviour of isolated chicks in a polarized maze precisely recovers the motory patterns subserving sensory invariance. Chicks actively seek for and explore ways to maintain invariance of internal states. They are looking for an ‘actor outside’, e.g. their own mirror image.
Paul Sheldon Davies
The Study of the Human Self: Affective Neuroscience and Philosophy
I discuss a few implications of theories in affective neuroscience, the work of Jaak Panksepp in particular, for philosophical reflections on the human self. As knowledge of the neural bases of our emotional systems develops, philosophers must adjust the substance and the methods of their investigations. They must, for instance, countenance the fact that our intuitive, pre-theoretical understanding of our agential capacities – the very phenomena about which philosophers typically theorize – often conflicts with what is known about the relevant neural processes. This is true with respect to all our capacities as deliberators, choosers, and actors, including our alleged capacity for free will and moral or legal responsibility.