TgF344-AD Rat Model of Alzheimer's Disease: Spatial Disorientation and Asymmetry in Hemispheric Neurodegeneration.

Background: The TgF344-AD ratline represents a transgenic animal model of Alzheimer's disease. We previously reported spatial memory impairment in TgF344-AD rats, yet the underlying mechanism remained unknown. We, therefore, set out to determine if spatial memory impairment in TgF344-AD rats is attributed to spatial disorientation.

Delay-dependent forgetting in object recognition and object location test is dependent on strain and test.

The object recognition and object location task (ORT and OLT, respectively) have been applied in preclinical research to evaluate the effects of treatments on memory. Although both tasks look quite similar, they differ with respect to the brain structures involved in the memory performance. The characterization of the memory performance in both tasks is important to understand treatment effects.

The Nucleus Basalis of Meynert and Its Role in Deep Brain Stimulation for Cognitive Disorders: A Historical Perspective.

The nucleus basalis of Meynert (nbM) was first described at the end of the 19th century and named after its discoverer, Theodor Meynert. The nbM contains a large population of cholinergic neurons that project their axons to the entire cortical mantle, the olfactory tubercle, and the amygdala. It has been functionally associated with the control of attention and maintenance of arousal, both key functions for appropriate learning and memory formation.

Subcortical electrophysiological activity is detectable with high-density EEG source imaging.

Subcortical neuronal activity is highly relevant for mediating communication in large-scale brain networks. While electroencephalographic (EEG) recordings provide appropriate temporal resolution and coverage to study whole brain dynamics, the feasibility to detect subcortical signals is a matter of debate. Here, we investigate if scalp EEG can detect and correctly localize signals recorded with intracranial electrodes placed in the centromedial thalamus, and in the nucleus accumbens.

Motivational Impairment is Accompanied by Corticoaccumbal Dysfunction in the BACHD-Tg5 Rat Model of Huntington's Disease.

Neuropsychiatric symptoms, such as avolition, apathy, and anhedonia, precede the onset of debilitating motor symptoms in Huntington's disease (HD), and their development may give insight into early disease progression and treatment. However, the neuronal and circuit mechanisms of premanifest HD pathophysiology are not well-understood. Here, using a transgenic rat model expressing the full-length human mutant HD gene, we find early and profound deficits in reward motivation in the absence of gross motor abnormalities.

Nucleus accumbens high-frequency stimulation selectively impacts nigrostriatal dopaminergic neurons.

High-frequency stimulation of the nucleus accumbens, also known as deep brain stimulation (DBS), is currently used to alleviate obsessive compulsive symptoms when pharmacotherapy is ineffective. However, the mechanism by which DBS achieves its therapeutic actions is not understood. Imaging studies and the actions of dopaminergic drugs in untreated patients suggest that the dopamine (DA) system likely plays a role in the pathophysiology of obsessive compulsive disorder.

Evaluation of animal models of obsessive-compulsive disorder: correlation with phasic dopamine neuron activity.

Obsessive compulsive disorder (OCD) is a psychiatric condition defined by intrusive thoughts (obsessions) associated with compensatory and repetitive behaviour (compulsions). However, advancement in our understanding of this disorder has been hampered by the absence of effective animal models and correspondingly analysis of the physiological changes that may be present in these models. To address this, we have evaluated two current rodent models of OCD; repeated injection of dopamine D2 agonist quinpirole and repeated adolescent injection of the tricyclic agent clomipramine in combination with a behavioural paradigm designed to produce compulsive lever pressing.

Attenuation of fear-like response by escitalopram treatment after electrical stimulation of the midbrain dorsolateral periaqueductal gray.

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) has frequently been shown to induce escape and freezing/decreased locomotion responses which mimic panic- and fear-like behaviour. In the present study we tested whether such spontaneous fear-like behaviour could be observed in an open-field test 12 h after dlPAG stimulation. Further, we tested whether this fear-like behaviour could be attenuated by acute or chronic administration of buspirone and escitalopram.

Nucleus accumbens and impulsivity.

The multifaceted concept of impulsivity implies that different impulsivity aspects, mediated by different neural processes, influence behavior at different levels. The nucleus accumbens (NAc) is a key component of the neural processes regulating impulsivity. In this review, we discuss the findings of lesion studies in animals and functional imaging studies in humans focusing on the role of the NAc in impulsivity.

Deep brain stimulation of the nucleus accumbens shell increases impulsive behavior and tissue levels of dopamine and serotonin.

The nucleus accumbens (NAc) is gaining interest as a target for deep brain stimulation (DBS) in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. In animal models, it has been shown that DBS of the NAc changes impulsive action.

Cerebellar nuclei are involved in impulsive behaviour.

Recent anatomical and clinical evidence has shown that the cerebellum, primarily considered a motor control structure, is also involved in higher cognitive functions and behavioural changes, such as impulsive behaviour. Impulsive behaviour has been shown in several studies to be increased by lesions of the mediodorsal (MD) thalamic nucleus. We performed deep brain stimulation (DBS) of the mediodorsal and ventrolateral (VL) thalamic nuclei in rats, clinically mimicking such a lesion, and tested them for changes in impulsive behaviour in a choice reaction time test.

Cognitive and limbic effects of deep brain stimulation in preclinical studies.

The use of deep brain stimulation (DBS) to control severely disabling neurological and psychiatric conditions is an exciting and fast emerging area of neuroscience. Deep brain stimulation has generally the same clinical effects as a lesion with respect to the improvement of clinical disability, but has more advantages such as its adjustability and reversibility. To this day, fundamental knowledge regarding the application of electrical currents to deep brain structures is far from complete.

Deep brain stimulation of the nucleus accumbens core and shell: opposite effects on impulsive action.

The nucleus accumbens is gaining interest as a target for deep brain stimulation in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. Here, we tested the hypothesis that stimulation of the nucleus accumbens core and shell would have different effects on impulsivity.