Abstract
The neurobiological basis of pathological anxiety and the improvement of its pharmacological treatment are a matter of intensive investigation. Here, using electrophysiological techniques in brain slices from animals of the high anxiety-related behavior (HAB) and normal anxiety-related behavior (NAB) mouse model, we show that basal neurotransmission at ventral hippocampal CA3-CA1 synapses is weaker in HAB compared to NAB mice. We further demonstrate that paired-pulse facilitation (PPF) and long-term potentiation (LTP) at these synapses are more pronounced in slices from HAB animals. Based on previous findings, we also examined whether intranasal delivery of neuropeptide S (NPS), which increasingly emerges as a potential novel treatment option for anxiety symptoms occurring in a variety of diseases like anxiety disorders, posttraumatic stress disorder, and major depression, impacts on the high-anxiety electrophysiological endophenotype in HAB mice. Strikingly, we detected enhanced basal neurotransmission and reduced PPF and LTP in slices from NPS-treated HAB animals. Collectively, our study uncovers a multifaceted high-anxiety neurophysiological endophenotype in the murine ventral hippocampus and provides the first evidence that an intranasally applied neuropeptide can shift such an endophenotype in an anxiety-regulating brain structure towards a “normal”-anxiety one.
Highlights
Anxiety symptoms occur in various psychiatric diseases, such as anxiety and depressive disorders [1] and schizophrenia [2], yet the neurophysiological basis of pathological anxiety remains poorly understood and improved pharmacotherapies are vitally needed [3,4]
As evident from the input-output curves depicted in Fig. 2A, basal neurotransmission was weaker in slices from high anxiety-related behavior (HAB) mice than in those obtained from normal anxiety-related behavior (NAB) animals (HAB (n = 20 slices / mice) vs. NAB (n = slices / 12 mice): two-way repeated measures ANOVA: Phenotype: F1,61 = 7.822, p = 0.009; Fiber volley amplitude (FVA): F2,61 = 314.055, p < 0.001; Phenotype x FVA: F2,61 = 1.084, p = 0.345; Tukey post hoc tests HAB vs. NAB, FVA 80, 120, 200 μV: p < 0.001)
Using electrophysiological techniques in acute hippocampal slices, we show that basal neurotransmission at ventral CA3-CA1 synapses is weaker in HAB compared to NAB mice
Summary
Anxiety symptoms occur in various psychiatric diseases, such as anxiety and depressive disorders [1] and schizophrenia [2], yet the neurophysiological basis of pathological anxiety remains poorly understood and improved pharmacotherapies are vitally needed [3,4]. Patent Application PCT/EP2012/056002 published October 4th, 2012 This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. We showed that intranasally applied NPS, which exerts anxiolytic-like effects, expands into the vHPC [13] Based on these facts and findings, we investigated here whether hyper- and “normally”-anxious mice [21] exhibit differences in neurotransmission and/or plasticity at ventral CA3-CA1 synapses and, since we detected such differences, whether intranasally administered NPS impacts on the high-anxiety endophenotype. We performed identical electrophysiological analyses in vHPC slices from HAB and NAB mice which were treated intranasally with NPS, to investigate for the first time whether vHPC electrophysiological properties are influenced by NPS in a similar way in pathological and normal anxiety states
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