LOCEN Research Topic: Psychobiology experiments on goal-directed behaviour with mice and rats

 

Research topic

Goal-directed behavior (GDB) is a fundamental means of animal adaptation. GDB involves behaviours sensitive to the value that the animal currently assignes to goals, and to the contingencies between goals and actions to accomplish them (Balleine and Dickinson, 1998). "Goals" can be defined as internal representations of an action outcome currently chosen as the target of the animal's behavior because its high motivational value (or incentive salience, Berridge, 2004). GDB is receiving increasing attention within the psychobiological community given its centrality for animal behaviour. The main brain components supporting GDB involve: the prefrontal cortex (PFC), important for higher-level cognition and encoding high-level features of goals; the nucleus accumbens (NAcc), at the vertex of the basalganglia hierachy; the amygdala (Amg), important for processing appetitive/aversive stimuli and the dopaminergic system, important for the neuromodulation of the overall GDB system. However, how the integrated system formed by these areas supports GDB is still debated. A working hypothesis on the system is that information on the value of stimuli, processed in Amg, are sent to the NAcc, and then NAcc, in loop with PFC, performs the selection of goals; goals then bias action selection involving lower basal ganglia-cortical loops (Burton et al., 2014; Mannella et al., 2013). A second aspect of GDB that calls for further investigations involves the type of rewards involved in the process. In this respect, current experiments on GDB commonly use appetitive stimuli (e.g., food pellets) or aversive stimuli (e.g., poisoned food) whose value is processed by areas such as the Amg, capable of assigning a value to previously neutral stimuli based on unconditioned stimuli (Corbit et al., 2001; Cardinal et al., 2002). Recently, Mannella et al. (2013) have proposed a novel hypothesis for which the value of goals can also depend on the novelty of action outcomes. The idea is that novel stimuli have a great biological salience as they might represent resources with a great value for the animal, or harmful or even lethal threats. For this reason, they should `ring an emergency bell' in the brain of the animal and immediatly recruit all its cognitive resources to carry out their further investigation. The main regions proposed to process novelty information is hippocampus (Hip) in which when novelty is detected, it promotes a strong production of dopamine (Lisman and Grace, 2005) regulating various brain areas, among which PFC, NAcc, Amg, and Hip itself. This research is directed to contribute to identify the architecture and functioning of the integrated brain system underlying goal-directed behavior, with particular attention to the way in which various motivational sources (i.e. novelty, appetitive, and aversive values) affect the normal and pathological functioning of the system.

Research specific problems
  • Understanding the brain system underlying goal-directed behaviour, in particular the role and interaction of the key brain areas forming it such as Amg,  Hip, NAcc, PFC, and the dopamine system.
  • Understanding the role and functioning of "novelty value'' in goal-directed behavior in normal conditions. Understanding the alterations of this system (both iperfunctioning or hypofunctioning) contributing to cause pathological conditions, e.g. role of vulnerability factors (as novelty/sensation-seekers) in addiction, compulsive gambling, compulsive/binge eating.
  • Understanding the neurobiological and motivational basis of diseases such as impulsive compulsive disorders (ICD), ADHD, addiction, and related medical problems such as dopamine-agonist effects in Parkinson's Disease. 
  • Formulating possible therapeutic applications based on innovative sophisticated technologies (e.g. optogenetics, deep brain stimulation) for diseases involving the motivational system (e.g., in addiction, ADHD, Parkinson).
Research method
  • Experiments with mice/rats. Behavioral experiments employ instrumental conditioning procedures as operant conditioning, Pavlovian to instrumental transfer (PIT), and Pavlovian procedures such as the Conditioned Place Preference (CPP) paradigm. Animal experiments involving inactivation and lesioning, and other more advanced techniques such as optogenetic.
  • The experiments will be carried out within collaborations involving research groups as those of Prof. Stefano Puglisi-Allegra and Prof. Simona Cabib (Dipartimento di Psicologia, Università di Roma “La Sapienza”).
Examples of research of this type carried out by the group

(see full references below)

  • Orsini, Bonito-Oliva, Conversi, Cabib (2005).
  • Orsini, C. Et al. (2004).
  • Cabib, Puglisi-Allegra (1994).
Requested motivations of the candidate
  • Strong interest in the topic and motivation to carry out research on it (very important)
  • Desire to acquire the knowledge and methods of the group
Requested knowledge of the candidate
  • University-level knowledge on cognitive psychology
  • University-level knowledge on psychobiology/neuroscience
Requested skills of the candidate
  • Capacity to read and understand scientific papers in English
  • Capacity to contribute to the design of behavioral animal experiments
  • Capacity to carry out experiments with animal in particular rodents
  • Capacity to contribute to write reports in English.
References
  • Balleine B. & Dickinson A. (1998). Goal-directed instrumental action: Contingency and incentive learning and their cortical substrates. In Neuroph., 37, 407-419.
    Berridge K. C. (2004). Motivation concepts in behavioral neuroscience. In Physiol. & Behav., 81, 179-209.
  • Burton A. C. et al. (2014). From ventral-medial to dorsal-lateral striatum: Neural correlates of reward-guided decision-making. In Neurob. Learn. Mem. May 21.
  • Cabib, S. & Puglisi-Allegra, S. (1994). Opposite responses of mesolimbic dopamine system to controllable and uncontrollable aversive experiences.. J Neurosci, 14 (5 Pt 2), 3333-3340. 
  • Cardinal R. N. et al.(2002). Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats. In Behav. Neuros. 116, 553–567.
  • Corbit L. H. et al. (2001). The role of the nucleus accumbens in instrumental conditioning: Evidence of a functional dissociation between accumbens core and shell. In J Neurosci., 21, 3251–3260.
  • Lisman J. et al. (2005). The hippocampal-VTA loop: controlling the entry of information into long-term memory. In Neuros., 34, 536–547.Mannella,F., Gurney, K., Baldassarre, G. (2013). The nucleus accumbens as a nexus between values and goals in goal-directed behavior: a review and a new hypothesis. In Front Behav Neurosci, 7 135.
  • Orsini, C.; Bonito-Oliva, A.; Conversi, D. & Cabib, S. (2005). Susceptibility to conditioned place preference induced by addictive drugs in mice of the C57BL/6 and DBA/2 inbred strains.. Psychopharmacology (Berl), 181 (2), 327-336. 
  • Orsini, C., Buchini, F., Piazza, P. V., Puglisi-Allegra, S. & Cabib, S. (2004). Susceptibility to amphetamine-induced place preference is predicted by locomotor response to novelty and amphetamine in the mouse. In Psychopharmacology (Berl), 172 (3), 264-270.