Abstract The dominance of one hemisphere for cognitive operations and decision making may be an efficient mechanism solving interhemispheric conflicts. To understand the ecological significance of the so-called metacontrol, we need better knowledge of its frequency and ontogenetic foundations. Since in pigeons, embryonic light experiences influence degree and direction of interhemispheric specialization and communication, it is conceivable that light affects metacontrol mechanisms. We therefore trained pigeons ( Columba livia ) with and without embryonic light stimulation in a colour discrimination task. Each eye/hemisphere learnt a different set of colours. After training, hemispheric-specific information was put into conflict and the analysis of conflict decision pattern allowed the identification of hemispheric dominance under binocular and monocular viewing conditions. A majority of pigeons displayed individual metacontrol independent of embryonic light experiences though not in the first test session. Reaction times indicate that interhemispheric mechanisms are critically involved in mediating the dominance of one hemisphere. The impact of interhemispheric components rises with increasing experience and even affects decision making under monocular seeing conditions. Overall results indicate that the hemispheres do not evaluate information independently and that interhemispheric communication in the pigeon brain is much stronger than previously thought and becomes more important with increasing experience.
Bipolar disorder is characterized by recurrent manic and depressive episodes. Patients suffering from this disorder experience dramatic mood swings with a wide variety of typical behavioral facets, affecting overall activity, energy, sexual behavior, sense of self, self-esteem, circadian rhythm, cognition, and increased risk for suicide. Effective treatment options are limited and diagnosis can be complicated. To overcome these obstacles, a better understanding of the neurobiology underlying bipolar disorder is needed. Animal models can be useful tools in understanding brain mechanisms associated with certain behavior. The following review discusses several pathological aspects of humans suffering from bipolar disorder and compares these findings with insights obtained from several animal models mimicking diverse facets of its symptomatology. Various sections of the review concentrate on specific topics that are relevant in human patients, namely circadian rhythms, neurotransmitters, focusing on the dopaminergic system, stressful environment, and the immune system. We then explain how these areas have been manipulated to create animal models for the disorder. Even though several approaches have been conducted, there is still a lack of adequate animal models for bipolar disorder. Specifically, most animal models mimic only mania or depression and only a few include the cyclical nature of the human condition. Future studies could therefore focus on modeling both episodes in the same animal model to also have the possibility to investigate the switch from mania-like behavior to depressive-like behavior and vice versa. The use of viral tools and a focus on circadian rhythms and the immune system might make the creation of such animal models possible.
Activation of the maternal immune system (MIA) during gestation is linked to neuropsychiatric diseases like schizophrenia. While many studies address behavioural aspects, less is known about underlying cellular mechanisms. In the following study, BALB/c mice received intraperitoneal injections of polyinosinic-polycytidylic acid (Poly I:C) (20 µg/ml) or saline (0.9%) at gestation day (GD) 9.5 before hippocampal neurons were isolated and cultured from embryonic mice for further analysis. Interestingly, strongest effects were observed when the perineuronal net (PNN) wearing subpopulation of neurons was analysed. Here, a significant reduction of aggrecan staining intensity, area and soma size could be detected. Alterations of PNNs are often linked to neuropsychiatric diseases, changes in synaptic plasticity and in electrophysiology. Utilizing multielectrode array analysis (MEA), we observed a remarkable increase of the spontaneous network activity in neuronal networks after 21 days in vitro (DIV) when mother mice suffered a prenatal immune challenge. As PNNs are associated with GABAergic interneurons, our data indicate that this neuronal subtype might be stronger affected by a prenatal MIA. Degradation or damage of this subtype might cause the hyperexcitability observed in the whole network. In addition, embryonic neurons of the Poly I:C condition developed significantly shorter axons after five days in culture, while dendritic parameters and apoptosis rate remained unchanged. Structural analysis of synapse numbers revealed an increase of postsynaptic density 95 (PSD-95) puncta after 14 DIV and an increase of presynaptic vesicular glutamate transporter (vGlut) puncta after 21 DIV, while inhibitory synaptic proteins were not altered.
A single chronic stress is often considered a potential reinforcer in psychiatric disorders. Lithium and ketamine both seem to ameliorate the consequences of stress. Here, male mice were either injected with lithium carbonate (LiCl), ketamine hydrochloride (KET), or sodium chloride (NaCl; controls) over nine consecutive days. Treatment was followed by 2 h of restraint stress over the first seven days. On the 9th day, 2 h after injection, all animals were tested in the open field, and novel object tests and behavior were analyzed using the toolbox ‘DeepLabCut’. To exclude an effect of generally altered locomotion activity on turning behavior, further parameters were assessed. Treatment before chronic stress exposure did not influence the total number of turns, nor the direction of turning behavior in the open field and the novel object test. Additionally, general locomotion did not differ. However, mice treated with LiCl showed a stronger turning bias (i.e., larger absolute lateralization quotients) in the novel object test when compared to mice treated with KET. This study underlines the potential of investigating turning behavior as a sensitive and reliable marker of stress reaction. Additionally, analyzing behavioral asymmetries in the context of psychopharmacological treatment can render new insights.
In this special issue, several aspects of animal models advancing our knowledge of mental disorders are covered.In history, there were relevant findings from animal research for psychiatry.The 'sedative' effect of lithium was first observed in guinea pigs.Initial tests with benzodiazepines showed sedative, muscle relaxant and anticonvulsant effects in mice, and a taming effect was reported in monkeys and lions.The fact that prolonged use of benzodiazepines can cause the development of tolerance was also first detected in animal studies.Even electroconvulsive therapy (ECT) was established in pigs and dogs.Mechanisms of extinction as an important application in psychotherapy have been largely studied in animal experiments.The main problem with animal studies is the transfer to the human situation especially in disease.Therefore, validity criteria of animal models were developed: (A) Face validity: Equality or comparability of humans and animals: same stimuli lead to the same responses.(B) Predictive validity: Prediction that a clinically effective medication will lead to changes in the behavior of the animal model analogous to its effect in humans.(C) Construct Validity: The neuropathological constructs that are thought to be responsible for the development of disease symptoms can also be represented in the model, e.g., by brain lesions.The prepulse inhibition (PPI) to an acoustical startle response e.g.demonstrates these validity criteria.Face Validity is given as PPI can be reliably triggered in many mammals and even birds.Various experimental interventions (pharmacological e.g. by NMDA antagonists, lesions in cortico-limbic-striatal network, rearing in social isolation) lead to a reduction of PPI similar to that in schizophrenic patients and therewith construct validity is given.Last but not least, predictive validity is confirmed as typical and atypical neuroleptics lead to the normalization of PPI.
