Physiological Profile of Neuropeptide Y-Expressing Neurons in Bed Nucleus of Stria Terminalis in Mice: State of High Excitability

Both, the anterior bed nucleus of the stria terminalis (BNST) and the neuropeptide Y (NPY) system are involved in shaping fear and defensive responses that adapt the organism to potentially life-threatening conditions. NPY is expressed in the BNST but NPY-expressing neurons in this critical hub in the stress response network have not been addressed before. Therefore, we performed whole-cell patch-clamp recordings in acute slices of anterior BNST from Npy-hrGFP transgenic mice to identify and characterize NPY-expressing neurons. We show that NPY-positive and NPY-negative neurons in anterior BNST match the previous classification scheme of type I (Regular Spiking), type II (Low-Threshold Bursting), and type III (fast Inward Rectifying) cells, although the proportion of these physiological phenotypes was similar within both neuronal subpopulations. However, NPY-positive and NPY-negative neurons possessed distinct intrinsic electrophysiological properties. NPY-positive neurons displayed higher input resistance and lower membrane capacitance, corresponding to small cell bodies and shorter less ramified dendrites, as compared to their NPY-negative counterparts. Furthermore, NPY-positive neurons generated higher frequent series of action potentials upon membrane depolarization and displayed significantly lower GABAA receptormediated synaptic responsiveness during evoked, spontaneous, and elementary synaptic activity. Taken together, these properties indicate an overall state of high excitability in NPY-positive neurons in anterior BNST. In view of the role of the anterior BNST in anxiety-and stress-related behaviors, these findings suggest a scenario where NPY-positive neurons are preferentially active and responsive to afferent inputs, thereby contributing to adaptation of the organism to stressful environmental encounters.