Towards chronic contextual conditioning in rats: The effects of different numbers of unpaired tone-shock presentations on freezing time and startle

Contextual conditioning in rats is typically quantified using freezing time or startle amplitude. In this study, we combined both anxiety measures in one procedure and systematically examined the effect of training with 0, 5, 10 or 15 unpaired tone-shock (0.8 mA - 250 ms) presentations on the expression of contextual conditioning in a chronic protocol with two training and testing days. Such a chronic procedure may be valuable as a chronic anxiety model. Training with 5, 10 or 15 explicitly unpaired shocks resulted in significant contextual freezing. There was no significant increase in freezing time from post-test 1 to post-test 2 and there were no differences between the three shocked groups, implying that the different numbers of shocks did not affect the degree of contextual freezing, probably because the ceiling freezing value had already been reached. Surprisingly, we observed no potentiated startle in the conditioned context. To summarize, our protocol produced consistent contextual freezing over two testing days.status: publishe

Optimization of a contextual conditioning protocol for rats using combined measurements of startle and freezing

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Histopathology after microelectrode recording and twelve years of deep brain stimulation

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Optimization of a contextual conditioning protocol for rats using combined measurements of startle amplitude and freezing: The effects of shock intensity and different types of conditioning

Contextual conditioning in rats is typically quantified using startle amplitude or freezing time. Our goal was to create a robust contextual conditioning protocol combining both startle amplitude and freezing time as measures of contextual anxiety. Comparison of 0.8 mA - 250 ms shocks with an established shock configuration (0.3 mA - 1 s) favoured the first parameters. Subsequently, we systematically investigated the effect of shock intensity (0.6 mA, 0.8 mA or 1.0 mA) and concurrently compared two different contextual conditioning procedures (shocks alone versus unpaired shock-tone presentations). In future experiments, this second type of contextual conditioning may form the optimal contrasting condition for a cued fear conditioning group, trained with explicit cue-shock pairings. The 0.8 mA shocks produced significant contextual freezing and startle potentiation, whereas the 0.6 mA and 1.0 mA shocks only led to a significant increase of freezing time. We found no major differences between the two types of conditioning, implying that these procedures might be equivalent. In conclusion, training with ten 0.8 mA - 250 ms shocks produced reliable contextual conditioning as measured with both startle amplitude and freezing time.status: publishe

Histological alterations induced by electrode implantation and electrical stimulation in the human brain: A review

Objectives. Electrical brain stimulation is used as a treatment for patients with intractable chronic pain and movement disorders. However, the implantation of electrodes and electrical stimulation may induce histological changes around the electrode tip. We aimed to review the histological changes in humans that were electrically stimulated in the brain. Methods. We traced 26 autopsy studies of which 19 patients received cerebellar stimulation and 37 patients deep brain stimulation.Results. Electrode implantation and electrical stimulation induced in part of the cases formation of a fibrous sheath around the electrode, loss of fairly large neurons, and limited gliosis. Macroscopic lesions were present in only some cases, mostly due to pulling at the extension cable in the postoperative evaluation period preceding definite implantation of the electrode wire and stimulator. Conclusions. Electrical brain stimulation induces histological changes in some patients. According to electrical brain stimulation studies in animals, these changes can be related to the charge and charge density per phase (and their interaction).status: publishe

Electrical stimulation in the lateral hypothalamus in rats in the activity-based anorexia model - Laboratory investigation

Object. One quarter of patients with anorexia nervosa have a poor outcome and continue to suffer chronically or die. Electrical brain stimulation may be of therapeutic benefit in some of these patients; however, the brain target for inducing symptom relief is unknown. In this study, the authors evaluated the effects of acute and chronic electrical stimulation in the lateral hypothalamus on food intake, locomotor activity, and survival time in rats in an activity-based anorexia model.status: publishe

Contextual conditioning in rats as an animal model for generalized anxiety disorder

Animal models of psychiatric disorders are important translational tools for exploring new treatment options and gaining more insight into the disease. Thus far, there is no systematically validated animal model for generalized anxiety disorder (GAD), a severely impairing and difficult-to-treat disease. In this review, we propose contextual conditioning (CC) as an animal model for GAD. We argue that this model has sufficient face validity (there are several symptom similarities), predictive validity (it responds to clinically effective treatments), and construct validity (the underlying mechanisms are comparable). Although the refinement and validation of an animal model is a never-ending process, we want to give a concise overview of the currently available evidence. We suggest that the CC model might be a valuable preclinical tool to enhance the development of new treatment strategies and our understanding of GAD.status: publishe

Anodal tDCS over the Primary Motor Cortex Facilitates Long-Term Memory Formation Reflecting Use-Dependent Plasticity

<div><p>Previous research suggests that anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) modulates NMDA receptor dependent processes that mediate synaptic plasticity. Here we test this proposal by applying anodal versus sham tDCS while subjects practiced to flex the thumb as fast as possible (ballistic movements). Repetitive practice of this task has been shown to result in performance improvements that reflect use-dependent plasticity resulting from NMDA receptor mediated, long-term potentiation (LTP)-like processes. Using a double-blind within-subject cross-over design, subjects (n=14) participated either in an anodal or a sham tDCS session which were at least 3 months apart. Sham or anodal tDCS (1 mA) was applied for 20 min during motor practice and retention was tested 30 min, 24 hours and one week later. All subjects improved performance during each of the two sessions (p < 0.001) and learning gains were similar. Our main result is that long term retention performance (i.e. 1 week after practice) was significantly better when practice was performed with anodal tDCS than with sham tDCS (p < 0.001). This effect was large (Cohen’s d=1.01) and all but one subject followed the group trend. Our data strongly suggest that anodal tDCS facilitates long-term memory formation reflecting use-dependent plasticity. Our results support the notion that anodal tDCS facilitates synaptic plasticity mediated by an LTP-like mechanism, which is in accordance with previous research.</p></div

Individual subject data.

<p>Individual subject data showing gains/savings measured during the retention test at day 7 compared to performance at the end of training (i.e. average performance at RT-D7-1…3 minus average performance at train8…10). Individuals exhibiting the same trend as the group average are shown in black. Only one subject (gray) exhibited better retention performance after practice with sham tDCS than after practice with anodal tDCS.</p