A Bittersweet Investigation of Availability and Nutritive Value as Determinants of Volitional Sucrose Consumption

Rats given ~24 h access to a 4% sucrose solution every 3rd day (E3DA) consume about 100 g more solution than rats with continuous, everyday access (EDA). Under the same EDA-E3DA conditions rats will consume similar amounts of a more concentrated 8 or 16% sucrose solutions (Eikelboom, Hewitt, & Adams, Unpublished). It maybe that with these more concentrated solutions rats hit a satiety limit that prevents a difference between EDA and E3DA consumption from being evident. Experiment 1 was conducted to investigate the effect of adding quinine to 4% and 8% sucrose solutions with the intention of reducing consumption to allow the emergence of an EDA-E3DA consumption difference with 8% sucrose. Rats were given EDA or E3DA access to 4% or 8% sucrose with or without added .005% quinine. An EDA-E3DA consumption difference emerged with 8% sucrose + .005% quinine where the quinine addition lowered consumption. However, in this experiment the EDA-E3DA consumption profile of 4% sucrose was smaller than typically seen. Rats show considerable variability in sucrose consumption and experiment 2 was conducted to explore the effects of using a pre-exposure period to determine group assignment. Rats were pre-exposed to 4% sucrose continuously for 6 days. Consumption during this pre-exposure was used to assign rats to 4% or 8% sucrose with or without added .005% quinine who were then assigned to EDA or E3DA conditions. In this experiment the pre-exposure helped create eight equal groups and the 4% sucrose group demonstrated an EDA-E3DA consumption difference. However, the .005% quinine concentration did not reduce 8% sucrose consumption as severely as it had in experiment 1 and failed to produce an EDA-E3DA difference with 8% sucrose. Experiment 3 explored the effects of a pre-exposure on 8% sucrose + .005% quinine consumption as a pre-exposure was a critical difference in the first two experiments. The results of experiment 3 suggested that a 4% sucrose pre-exposure would not change future 8% sucrose + .005% quinine consumption levels. Experiment 4 was conducted to investigate the effect of varying the quinine concentration on 8% sucrose + quinine consumption. Rats were given EDA or E3DA to 8% sucrose adulterated with .0025%, .005%, .01%, or .02% quinine. Quinine concentration-dependently reduced consumption levels, and allowed for an EDA-E3DA consumption difference to emerge. Collectively these experiments suggest that rats’ regulate their consumption of a supplementary sucrose solution based on the value of the solution and its availability in an integrated fashion. That is, the ability for intermittent access to elevate consumption depends on the value of the food being consumed. This is evidenced by the efficacy of quinine adulteration to degrade the value, and consequently intake, of an 8% sucrose solution which permitted an EDA-E3DA difference, normally only seen with 4% sucrose, to emerge

Perception meets action: fMRI and behavioural investigations of human tool use

Tool use is essential and culturally universal to human life, common to hunter-gatherer and modern advanced societies alike. Although the neuroscience of simpler visuomotor behaviors like reaching and grasping have been studied extensively, relatively little is known about the brain mechanisms underlying learned tool use. With learned tool use, stored knowledge of object function and use supervene requirements for action programming based on physical object properties. Contemporary models of tool use based primarily on evidence from the study of brain damaged individuals implicate a set of specialized brain areas underlying the planning and control of learned actions with objects, distinct from areas devoted to more basic aspects of visuomotor control. The findings from the current thesis build on these existing theoretical models and provide new insights into the neural and behavioural mechanisms of learned tool use. In Project 1, I used fMRI to visualize brain activity in response to viewing tool use grasping. Grasping actions typical of how tools are normally grasped during use were found to preferentially activate occipitotemporal areas, including areas specialized for visual object recognition. The findings revealed sensitivity within this network to learned contextual associations tied to stored knowledge of tool-specific actions. The effects were seen to arise implicitly, in the absence of concurrent effects in visuomotor areas of parietofrontal cortex. These findings were taken to reflect the tuning of higher-order visual areas of occipitotemporal cortex to learned statistical regularities of the visual world, including the way in which tools are typically seen to be grasped and used. These areas are likely to represent an important source of inputs to visuomotor areas as to learned conceptual knowledge of tool use. In Project 2, behavioural priming and the kinematics of real tool use grasping was explored. Behavioural priming provides an index into the planning stages of actions. Participants grasped tools to either move them, grasp-to-move (GTM), or to demonstrate their common use, grasp-to-use (GTU), and grasping actions were preceded by a visual preview (prime) of either the same (congruent) or different (incongruent) tool as that which was then acted with. Behavioural priming was revealed as a reaction time advantage for congruent trial types, thought to reflect the triggering of learned use-based motor plans by the viewing of tools at prime events. The findings from two separate experiments revealed differential sensitivity to priming according to task and task setting. When GTU and GTM tasks were presented separately, priming was specific to the GTU task. In contrast, when GTU and GTM tasks were presented in the same block of trials, in a mixed task setting, priming was evident for both tasks. Together the findings indicate the importance of both task and task setting in shaping effects of action priming, likely driven by differences in the allocation of attentional resources. Differences in attention to particular object features, in this case tool identity, modulate affordances driven by those features which in turn determines priming. Beyond the physical properties of objects, knowledge and intention of use provide a mechanism for which affordances and the priming of actions may operate. Project 3 comprised a neuroimaging variant of the behavioural priming paradigm used in Project 2, with tools and tool use actions specially tailored for the fMRI environment. Preceding tool use with a visual preview of the tool to be used gave rise to reliable neural priming, measured as reduced BOLD activity. Neural priming of tool use was taken to reflect increased metabolic efficiency in the retrieval and implementation of stored tool use plans. To demonstrate specificity of priming for familiar tool use, a control task was used whereby actions with tools were determined not by tool identity but by arbitrarily learned associations with handle color. The findings revealed specificity for familiar tool-use priming in four distinct parietofrontal areas, including left inferior parietal cortex previously implicated in the storage of learned tool use plans. Specificity of priming for tool-action and not color-action associations provides compelling evidence for tool-use-experience-dependent plasticity within parietofrontal areas

Human posterior parietal cortex mediates hand-specific planning

The processes underlying action planning are fundamental to adaptive behavior and can be influenced by recent motor experience. Here, we used a novel fMRI Repetition Suppression (RS) design to test the hypotheses that action planning unfolds more efficiently for successive actions made with the same hand. More efficient processing was predicted to correspond with both faster response times (RTs) to initiate actions and reduced fMRI activity levels � RS. Consistent with these predictions, we detected faster RTs for actions made with the same hand and accompanying fMRI-RS within bilateral posterior parietal cortex and right-lateralized parietal operculum. Within posterior parietal cortex, these RS effects were localized to intraparietal and superior parietal cortices. These same areas were more strongly activated for actions involving the contralateral hand. The findings provide compelling new evidence for the specification of action plans in hand-specific terms, and indicate that these processes are sensitive to recent motor history. Consistent with computational efficiency accounts of motor history effects, the findings are interpreted as evidence for comparatively more efficient processing underlying action planning when successive actions involve the same versus opposite hand

The role of dopaminergic projections from the ventral tegmental area to the nucleus accumbens core and shell in responding to a discrete alcohol cue in different contexts

Environmental stimuli that predict alcohol are powerful triggers for relapse in humans. These stimuli become established as alcohol cues through Pavlovian conditioning and can be grouped into discrete cues (e.g. smell, sight, taste of alcohol) and contexts (e.g. bar). In the current thesis, a Pavlovian conditioning with context alternation procedure was used to measure the capacity for an alcohol-associated context (alcohol context) to influence responding to a discrete alcohol conditioned stimulus (CS). Responding to a discrete alcohol CS was elevated in an alcohol context compared to an equally familiar neutral context. By incorporating other behavioural procedures, the influence of context over responding to a discrete alcohol CS was shown to be persistent and temporally sensitive. Pharmacology and chemogenetic approaches revealed that dopamine neurotransmission and the activity of ventral tegmental area (VTA) dopamine neurons was necessary for responding to a discrete alcohol CS in a neutral context. Further, chemogenetic inhibition of the dopaminergic projection from the VTA to the nucleus accumbens (NAc) core reduced CS responding in the alcohol and neutral context. Differently, chemogenetic inhibition of the dopaminergic projection from the VTA to the NAc shell selectively reduced CS responding in the alcohol context, and not in the neutral context. Thus, the dopaminergic VTA-to-NAc core projection was necessary for responding to a discrete alcohol CS whereas the dopaminergic VTA-to-NAc shell projection was necessary for the elevation of this behaviour in an alcohol context. Targeting of tyrosine hydroxylase (TH) positive VTA dopamine neurons and the use of chemogenetics to manipulate neural activity in a circuit-specific manner were validated using immunocytochemistry and electrophysiology, respectively. Chemogenetic designer receptors were selectively (~95%) expressed in TH positive VTA neurons. Chemogenetic inhibition or excitation of VTA dopamine terminals in the NAc modulated the amplitude of electrically-evoked excitatory postsynaptic currents in NAc core medium spiny neurons (MSNs). Thus, a circuit-specific chemogenetic approach could be used to target VTA dopamine neurons and bidirectionally affect the activity of postsynaptic MSNs. Based on the finding that the VTA-to-NAc shell projection was necessary for the elevation of CS responding in the alcohol context, the sufficiency of activating VTA dopamine neurons and their projection to the NAc shell to drive CS responding was tested. Chemogenetic activation of VTA dopamine neurons failed to impact responding to a discrete alcohol CS in a neutral context, despite affecting feeding behaviour in the same rats. Further, chemogenetic activation of the dopaminergic VTA-to-NAc shell projection failed to affect CS responding in the alcohol and neutral context. Thus, chemogenetic activation of VTA dopamine neurons or their projections to the NAc shell was not sufficient to elevate responding to a discrete alcohol CS. The lack of an effect of activating dopaminergic substrates on responding to a discrete alcohol CS suggested that non-dopaminergic circuits are recruited to elevate responding to a discrete alcohol CS in an alcohol context. This hypothesis was examined by microinfusing a glutamate-like agonist in the NAc shell during tests for CS responding in the neutral and alcohol context. Responding to a discrete alcohol CS was selectively reduced by microinfusion of a glutamate-like agonist in the alcohol context and was unaffected in the neutral context. This selective effect on CS responding in the alcohol context implicates glutamatergic activity in the NAc shell in the influence of context over responding to a discrete alcohol CS. In summary, responding to a discrete alcohol CS is elevated in an alcohol context and the influence of context over this behaviour is persistent and temporally sensitive. Responding to a discrete alcohol CS requires the activity of VTA dopamine neurons and their projections to the NAc core. The elevation of responding to a discrete alcohol CS in an alcohol context requires the dopaminergic projection from the VTA to the NAc shell. Attempts to elevate responding to a discrete alcohol CS by activating dopaminergic or glutamatergic substrates either failed to affect or reduced CS responding, respectively. Thus, the circuits sufficient to elevate responding to a discrete alcohol CS may involve the coordinated activation of dopaminergic and glutamatergic inputs to the NAc shell. Ultimately, a detailed description of the circuits that mediate the influence of discrete cues and contexts over responding for alcohol will inform the development of efficacious behavioural and pharmacological therapies for alcohol use disorder

Hand choice is unaffected by high frequency continuous theta burst transcranial magnetic stimulation to the posterior parietal cortex

The current study used a high frequency TMS protocol known as continuous theta burst stimulation (cTBS) to test a model of hand choice that relies on competing interactions between the hemispheres of the posterior parietal cortex. Based on the assumption that cTBS reduces cortical excitability, the model predicts a significant decrease in the likelihood of selecting the hand contralateral to stimulation. An established behavioural paradigm was used to estimate hand choice in each individual, and these measures were compared across three stimulation conditions: cTBS to the left posterior parietal cortex, cTBS to the right posterior parietal cortex, or sham cTBS. Our results provide no supporting evidence for the interhemispheric competition model. We find no effects of cTBS on hand choice, independent of whether the left or right posterior parietal cortex was stimulated. Our results are nonetheless of value as a point of comparison against prior brain stimulation findings that, in contrast, provide evidence for a causal role for the posterior parietal cortex in hand choice