<p>Finding and consuming food and water are among the most critical functions for an animal's survival. Food seeking (e.g., exploration and approach) and consummatory (e.g., licking, chewing, swallowing) behaviors are usually highly controlled, resulting in stable food intake, body mass, and fat stores in humans and laboratory animals. These variables are thought to be governed by homeostatic control systems that closely regulate many aspects of feeding behavior. However, the homeostatic mechanisms underlying these processes are often disrupted in humans, resulting in either hyperphagia or hypophagia. Despite many decades of investigations into the regulatory circuits of animals and humans, the neural circuits that underlie voluntary feeding are unclear. There have been considerable advances into understanding how the brain is able to broadly regulate food consumption (e.g., the role of circulating hormones on food intake and body weight). As much work has focused on hypothalamic mechanisms, relatively little is known about how other neural systems contribute to specific aspects of food seeking and consumption. </p><p> The basal ganglia have been implicated in many aspects of motivated behavior including appetitive and consummatory processes. However, the precise role that basal ganglia pathways play in these motivated behaviors remain largely unknown. One reason for this is that the basal ganglia are functionally and anatomically heterogeneous, with distinct functional circuit elements being embedded within overlapping tissue. Until recently, tools permitting identification and manipulation of molecularly defined neuron populations were unavailable. </p><p> The following experiments were designed to assess the role of the basal ganglia in regulating appetitive and consummatory behavior in mice. The first experiment (Chapter 2) examines the relationship between neural activity in the substantia nigra¬, a¬ major output nucleus of the basal ganglia, and an animal's motivational state. Both dopaminergic and GABAergic neurons show bursts of action potentials in response to a cue that predicts a food reward in hungry mice. The magnitude of this burst response is bidirectionally modulated by the animal's motivational state. When mice are sated prior to testing, or when no pellets can be consumed, both motivational state and bidirectional modulation of the cue response are unchanging. </p><p> The second set of experiments (Chapter 3 and 4) utilizes a mouse model of hyperdopaminergia: Dopamine transporter knockout mice. These mice have persistently elevated synaptic dopamine. Consistent with a role of dopamine in motivation, hyperdopaminergic mice exhibit enhanced food seeking behavior that is dissociable from general hyperactivity. Lentiviral restoration of the dopamine transporter into either the dorsolateral striatum or the nucleus accumbens, but not the dorsomedial striatum, is sufficient to selectively reduce excessive food seeking. The dopamine transporter knockout model of hyperdopaminergia was then used to test the role of dopamine in consummatory processes, specifically, licking for sucrose solution. Hyperdopaminergic mice have higher rates of licking, which was due to increased perseveration of licking in a bout. By contrast, they have increased individual lick durations, and reduced inter-lick-intervals. During extinction, both knockout and control mice transiently increase variability in lick pattern generation while reducing licking rate. Yet they show very different behavioral patterns. Control mice gradually increase lick duration as well as variability in extinction. By contrast, dopamine transporter knockout mice exhibited more immediate (within 10 licks) adjustments--an immediate increase in lick duration variability, as well as more rapid extinction. These results suggest that the level of dopamine can modulate the persistence and pattern generation of a highly stereotyped consummatory behavior like licking, as well as new learning in response to changes in environmental feedback. </p><p> The final set of experiments was designed to test the relationship between consummatory behavior and the activity of GABAergic basal ganglia output neurons projecting from the substantia nigra pars reticulata to the superior colliculus, an area that has been implicated in regulating orofacial behavior. Electrophysiological recording from mice during voluntary drinking showed that activity of GABAergic output neurons of the substantia nigra pars reticulata reflect the microstructure of consummatory licking. These neurons exhibit oscillatory bursts of activity, which are usually in phase with the lick cycle, peaking near the time of tongue protrusion. Dopaminergic neurons, in contrast, did not reflect lick microstructure, but instead signaled the boundaries of a bout of licking. Neurons located in the lateral part of the superior colliculus, a region that receives direct input from GABAergic projection neurons in the substantia nigra pars reticulata, also reflected the microstructure of licking with rhythmic oscillations. These neurons, however, showed a generally opposing pattern of activity relative to the substantia nigra neurons, pausing their firing when the tongue is extended. To test whether perturbation of the nigrotectal pathway could influence licking behavior, channelrhodopsin-2 was selectively expressed in GABAergic neurons of the substantia nigra and the axon terminals within the superior colliculus were targeted with optic fibers. Activation of nigrotectal neurons disrupted licking in a frequency-dependent manner. Using optrode recordings, I demonstrate that nigrotectal activation inhibits neurons in the superior colliculus to disrupt the pattern of licking. </p><p> Taken together, these results demonstrate that the basal ganglia are involved in both appetitive and consummatory behaviors. The present data argue for a role of striatonigral dopamine in regulating general appetitive responding: persistence of food-seeking. Nigraltectal GABA neurons appear to be critical for consummatory orofacial motor output.</p> / Dissertation

Thesis (Ph. D.)--Virginia Commonwealth University, 2008. / Prepared for: Dept. of Pharmacology and Toxicology. Bibliography: leaves 153 - 179. Available online via the internet.

Honey bees can form distinct spatiotemporal memories that allow them to return repeatedly to different food sources at different times of day. Although it is becoming increasingly clear that different behavioral states are associated with different profiles of brain gene expression, it is not known whether this relationship extends to states that are as dynamic and specific as those associated with foraging-related spatiotemporal memories. We tested this hypothesis by training different groups of foragers from the same colony to collect sucrose solution from one of two artificial feeders; each feeder was in a different location and had sucrose available at a different time, either in the morning or afternoon. Bees from both training groups were collected at both the morning and afternoon training times to result in one set of bees that was undergoing stereotypical food anticipatory behavior and another that was inactive for each time of day. Between the two groups with the different spatiotemporal memories, microarray analysis revealed that 1329 genes were differentially expressed in the brains of honey bees. Many of these genes also varied with time of day, time of training or state of food anticipation. Some of these genes are known to be involved in a variety of biological processes, including metabolism and behavior. These results indicate that distinct spatiotemporal foraging memories in honey bees are associated with distinct neurogenomic signatures, and the decomposition of these signatures into sets of genes that are also influenced by time or activity state hints at the modular composition of this complex neurogenomic phenotype.

Thesis advisor: Michael Numan / Maternal behavior is a primary social characteristic of mammals. By studying maternal behavior in rats, broader inferences can be made about the neural circuits that influence maternal behavior in other mammals, including humans. Maternal behavior of rats includes nest building, pup grooming, nursing, and pup retrieval. The projections from the medial preoptic area of the hypothalamus (MPOA) to the ventral tegmental area (VTA) of the mesolimbic dopamine system are known to regulate maternal behavior in post-partum rats. The aim of the present study was to examine how inhibition of the basolateral amygdala (BLA), an area that projects to the nucleus accumbens-ventral palldium (NA-VP) circuit of the mesolimbic dopamine system, bilaterally with muscimol (a GABA-A agonist) might interrupt the retrieval of pups by post-partum rats. Females injected with muscimol, but not those injected with saline, displayed significant deficits in retrieval behavior, suggesting that the BLA is a region important for the promotion of maternal behavior. The effects were also reversible, as all females displayed normal maternal behavior 24-hours post-injection. Follow-up studies should use asymmetric neuron-specific lesions of the BLA and the VP to show that the projections from the BLA to the VP are essential for maternal behavior. / Thesis (BA) — Boston College, 2010. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Psychology Honors Program. / Discipline: Psychology.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Für alle Tiere ist die Nahrungsaufnahme ein überlebenswichtiger Vorgang. Das konsumatorische Verhalten ist Teilaspekt eines homöostatischen Prozesses. Ausgelöst wird konsumatorisches und appetitives Verhalten durch interne, motivationale Zustände. Die internen Zustände „gesättigt“ und „ungesättigt“ werden bei vielen Tierarten durch ein Wechselspiel zwischen orexigen- und anorexigen-wirkenden Neuropeptiden vermittelt. Um die zentralnervöse Steuerung von Appetit und Sättigung genauer zu klären, wurde in dieser Studie die schwarzbäuchige Taufliege Drosophila melanogaster als Modellorganismus genutzt. Dabei konnte gezeigt werden, dass durch eine artifizielle, thermogenetisch induzierte Aktivierung von Neuronen, welche das Neuropeptid SIFamid exprimieren, das Verhalten der Insekten verändert wird. Die Tiere zeigen vermehrte Nahrungsaufnahme und sind motivierter, auf appetitive gustatorische und olfaktorische Reize zu reagieren. Des Weiteren wurden Hinweise gesammelt, dass das Neuropeptid SIFamid keinen inhibitorischen Einfluss auf das Balzverhalten der Taufliegen ausübt. Mit immunhistochemischen Färbungen konnte gezeigt werden, dass die Dendriten der SIFamidergen Neurone in unmittelbarer Nähe zu den Axonendigungen von Neuronen, die orexigen- oder anorexigen-wirkende Neuropeptide produzieren, liegen. Dieser Befund lässt auf ein mögliches Zusammenspiel zwischen den diversen peptidergen Neuronen schließen. Mit Hilfe der split-GFP-Technik konnte das peptiderge Netzwerk der SIFamidergen Neurone detaillierter untersucht werden. Es wurde gefunden, dass die SIFamidergen Neurone in enger räumlicher Nachbarschaft zu Neuronen, die in die Nahrungsaufnahme sowie die nervöse Steuerung des Metabolismus involviert sind, stehen. In Kombination mit einem zweiten, unabhängigen Expressionssystem konnten die SIFamidergen Neurone thermogenetisch depolarisiert werden und die neuronale Antwort der olfaktorischen Rezeptorneurone auf Duftstimuli in den Antennalloben mit Hilfe von in-vivo Calcium Imaging untersucht werden. Es konnte dadurch gezeigt werden, dass die neuronale Aktivität in den Duftsinneszellen erhöht ist. Aufgrund vorliegender Daten aus Anatomie, Verhaltensexperimenten und in-vivo Calcium Imaging lässt sich schlussfolgern, dass SIFamid ein bis dato unbekannter „Mitspieler“ bei der Steuerung der Nahrungsaufnahme ist und modulierend auf sensorische neuronale Schaltkreise sowie insgesamt appetitfördernd auf die Taufliege wirkt.

Understanding the mechanisms of memory is vital in making sense of the continuity of the self, our experience of time and of the relation between mind and body. The invertebrate Drosophila melanogaster offers us an opportunity to study and comprehend the overwhelming complexity of memory on a smaller scale. The work presented here investigates the neural circuitry in the fly brain required for olfactory memory processing. Our observation that Dorsal Paired Medial (DPM) neurons, which project only to mushroom body (MB) neurons, are required during memory storage but not for acquisition or retrieval, led us to revisit the role of MB neurons in memory processing. We show that neurotransmission from the α'β' subset of MB neurons is required to acquire and stabilize aversive and appetitive odor memory but is dispensable during memory retrieval. In contrast neurotransmission from MB αβ neurons is only required for memory retrieval. These data suggest a dynamic requirement for the different subsets of MB neurons in memory and are consistent with the notion that recurrent activity in a MB α'β' neuron-DPM neuron loop is required to consolidate memories formed in the MB αβ neurons. Furthermore, we show that a single two-minute training session pairing odor with an ethologically relevant sugar reinforcement forms long-term appetitive memory that lasts for days. This robust, stable LTM is protein-synthesis-, Creb- and radish-dependent and relies on the activity in the DPM neuron and mushroom body α'β' neuron circuit during the first hour after training and mushroom body αβ neuron output during retrieval. Lastly, experiments feeding and/or starving flies after training reveals a critical motivational drive that enables memory retrieval. Neural correlates of motivational states are poorly understood, but using our assay we found a neural mechanism that accounts for this motivation-state-dependence. We demonstrate a role for the Neuropeptide F (dNPF) circuitry, which led to the identification of six dopaminergic MB-MP neurons that innervate the mushroom bodies as being critical for appetitive memory performance. Directly blocking the MB-MP neurons releases memory performance in fed flies whereas stimulating them suppresses memory performance in hungry flies. These studies provide us with an enhanced knowledge of systems level memory processing in Drosophila.