Electrical stimulation and recording in the bed nucleus of the stria terminalis in a rat model of anxiety (poster)

Objectives Multiple studies have implied a pivotal role for the bed nucleus of the stria terminalis (BST) within the anxiety network. Previously, our research group showed that the BST is hyperactive in anxious rats, that electrolytic lesions reduce the expression of conditioned anxiety and that high-frequent stimulation (HFS) in this brain region alleviates symptoms in obsessive-compulsive disorder. The aims of our current study are two-fold. First, we hypothesized that HFS (>100 Hz) in the BST reduces the expression of conditioned anxiety (Experiment (Exp) 1). Secondly, we aimed to scrutinize neuronal BST activity during anxious and non-anxious states in our model (Exp2). Materials & Methods Exp1: Electrodes and cannulas were implanted in male Wistar rats, targeting the BST region. After recovery, all animals were conditioned to a context in which they received electric footshocks. On the next day, the animals were re-exposed to this context, and contextual anxiety was quantified through freezing and startle measurements. Rats either received BST lesions one day earlier (LES; n=9); electrical BST stimulation during the test session (STIM; n=13); or no intervention (CTRL; n=12). Finally, an open field test was conducted to evaluate effects of BST manipulations on non-conditioned anxiety and motor behavior. Exp2: Male Wistar rats were implanted with bipolar recording electrodes in the BST. All animals underwent context conditioning as described for Exp1, with or without shock administration during training (ANX; n=14 and CTRL; n=13, respectively). Local field potentials (LFPs) were recorded during baseline and test sessions. Results Exp1: We found that LES rats displayed significantly reduced freezing and startle measurements compared to CTRL rats. Interestingly, freezing values were lower in STIM vs. CTRL, indicating anxiolytic effects of stimulation. BST interventions did not affect unconditioned anxiety or motor behavior in an open field. Exp2: Preliminary analyses showed significant differences in low-frequency band power between anxious and non-anxious states. Discussion We find that HFS in the BST produces anxiolytic effects, albeit to a lesser extent than those obtained by ablative surgery. Furthermore, we demonstrated altered neuronal BST activity during anxious states in our rat model, which may be used to improve stimulation effects in future experiments (e.g. closed-loop stimulation). Our findings underline the therapeutic potential of HFS in the BST for disorders which are hallmarked by pathological anxiety. Further research will be necessary to assess the translatability of these findings to the clinic. Conclusions In summary, we showed that (1) electrical BST stimulation reduces anxiety and that (2) the BST displays altered neural activity during anxious states in our rat model.status: publishe