Aufgabe der elektrophysiologischen Studie zur Charakterisierung der neuronalen hypothalamischen Plastizität beim Haushuhn war es, den Einfluss des Alters sowie GABAerger Substanzen auf die Feuerrate und die Temperatursensitivität (thermischer Koeffizient: TC) von Hypothalamusneuronen mittels extrazellulärer Ableitungen in Hirnschnitten zu untersuchen. Im Vergleich zu adulten Vögeln und Säugetieren wurde bei juvenilen Hühnern eine hohe neuronale Kältesensitivität nachgewiesen, die offensichtlich eine spezifische Eigenschaft juveniler Vögel ist. Die Ontogenese der neuronalen hypothalamischen Thermosensitivität ist deutlich artspezifisch. Einige Neurone wiesen eine inherente Kältesensitivität auf. Eine mögliche zentrale Rolle kältesensitiver Neurone im Rahmen der Thermoregulation juveniler Hühner wurde postuliert. Muscimol und Baclofen hemmen signifikant die Feuerrate der Hypothalamusneurone, unabhängig von der jeweiligen Thermosensitivität. Demgegenüber bewirken Bicucullin und CGP35348 einem Anstieg der Feuerrate. Nur bei kältesensitiven Neuronen wurde der TC signifikant durch GABAB-Rezeptor-Liganden verändert (signifikant erhöht durch Baclofen und durch CGP35348 gehemmt). Der Effekt von Muscimol und Baclofen auf Feuerrate und TC wurde durch Co-Perfusion mit einer 10-fach höheren Konzentration der entsprechenden Antagonisten Bicucullin und CGP35348 aufgehoben. Der wesentliche GABAerge Einfluss auf thermosensitive und –insensitive Hypothalamusneurone ist mit dem bei Säugetieren nachgewiesenen vergleichbar. Der einzige Unterschied betrifft die GABAB-Rezeptor vermittelte Änderung des TC. Beim Hühnerküken betraf dies die kältesensitiven und beim Säugetier die wärmesensitiven Neurone. Der grundlegende Mechanismus der GABAergen Beeinflussung thermosensitiver und –insensitiver Neurone scheint einen älteren evolutionären Ursprung zu haben. Eine funktionelle Rolle GABAerger Substanzen im Rahmen der zentralen Kontrolle der Körpertemperatur beim Vogel ist möglich. / In the present electrophysiological studies, characterization of neuronal hypothalamic plasticity in the chicken aims to investigate the influence of age during development by extracellular recordings. High neuronal cold sensitivity has been found in juvenile chicken in contrast to adult mammals and birds. High hypothalamic cold sensitivity seems to be a specific characteristic feature in juvenile birds. Between species a species specificity of the early development of neuronal hypothalamic thermosensitivity could be clearly demonstrated. Existence of inherent nature to a certain degree suggests a possible thermoregulatory role of cold-sensitive neurons in chicken. The effects of the GABAergic substances on neuronal tonic activity (firing rate) and temperature sensitivity (temperature coefficient) in hypothalamic neurons have been examined. Muscimol and baclofen in equimolar concentrations significantly inhibited tonic activity, regardless of their type of thermosensitivity. In contrast bicuculline and CGP 35348 increased firing rate. Temperature coefficient was significantly changed by ligands of GABAB receptors, restricted to cold-sensitive neurons. The TC was significantly increased by baclofen and significantly decreased by CGP 35348. Effects of muscimol and baclofen on firing rate and TC were prevented by co-perfusion of appropriate antagonists bicuculline and CGP 35348, respectively in tenfold higher concentration. Thus the main effects of GABA in chicken are similar with that described in mammals. The only difference is in respect of the GABAB receptors mediated change restricted to cold-sensitive neurons in chicken but in mammals only seen in warm-sensitive neurons. However, the results indicate that the fundamental mechanism of GABAergic influence in chicken are conserved during evolution. The response of hypothalamic neurons to temperature changes suggest a possible functional role of GABAergic substances in the control of body temperature in birds.

This thesis extends the understanding of the neural and neurochemical contributions to two forms of behavioural adaptation, reversal learning and contingency degradation, in which stimulus/action-reward contingencies are altered. The results are interpreted within the psychological framework of the compulsivity construct, and their implications for the pathological behaviour of obsessive-compulsive-disorder (OCD) are considered. The orbitofrontal cortex (OFC) and striatum are key brain structures involved in reversal learning, as are the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) within those respective regions. However, there has been little empirical evidence of how these two structures and neurochemical systems interact, especially in the functional context of reversal learning. In Chapter Three, the impact of experimentally-induced reductions of 5-HT in the anterior OFC on monoamine levels in subcortical structures such as the striatum and amygdala was determined, DA being found to be significantly up-regulated in the amygdala. Functionally, 5-HT depletion of the OFC has previously been shown to induce deficits in reversal learning. To determine the possible causal significance of amygdala dopamine up-regulation for said reversal learning deficit, the effects of blocking the upregulation with the infusion of intra amygdala DA receptor antagonists following bilateral OFC 5-HT depletion were investigated in a reversal learning paradigm. In Chapter Four, the differential roles of regions of striatum were examined in visual reversal learning. Two recent investigations in non-human primates highlighted the role of the striatum in reversal learning,but pinpointed the critical region to be either the ventromedial caudate or the putamen. Marmosets were trained on a serial reversal task that allowed multiple acute neural manipulations, and the ventromedial caudate and putamen were then reversibly inactivated using the GABAA agonist muscimol. Results indicated dose-related impairments specifically in reversal learning within the putamen, with sparing of discrimination retention. By contrast, similar reversible inactivation of the caudate nucleus produced marked deficits in visual discrimination performance (retention). In Chapter Five, the neural basis of action-outcome contingency knowledge was investigated by inactivating distinct regions of the PFC, the perigenual ACC (pgACC; area 32) and the anterior OFC, and determining response sensitivity to the degradation of action-outcome contingencies. In previous work, excitotoxic lesions of either the pgACC or the OFC had been found to induce insensitivity to contingency degradation in marmosets. However, the design of that experiment did not allow specification of whether stimulus- or action-outcome associations were disrupted, and a precise neural locus could not be determined for the behavioural effects as the OFC lesions included parts of the lateral and medial OFC. I therefore developed a novel contingency degradation paradigm that distinguished between stimulus- and action-outcome associations to enable the study of acute pharmacological manipulations in both brain regions. The pgACC and OFC were reversibly inactivated using GABAA-GABAB agonists (muscimol-baclofen). Whereas the pgACC inactivation produced selective deficits in sensitivity to action-outcome contingency degradation, OFC inactivation reduced the suppressive effect of noncontingent reward on responding more generally but left intact sensitivity to degradation of the contingencies. These results are discussed in terms of different theories of the functions of the pgACC and OFC. In the final discussion the findings on the neural substrates of reversal learning and contingency degradation are drawn together in terms of their significance for theories of PFC involvement in cognitive control, and for the understanding of OCD and other neuropsychiatric disorders.