Post-traumatic stress disorder (PTSD) is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic) are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma.
Rodríguez-Sierra OE, Turesson HK, Pare D. Contrasting distribution of physiological cell types in different regions of the bed nucleus of the stria terminalis. J Neurophysiol 110: 2037-2049. First published August 7, 2013 doi:10.1152/jn.00408.2013.-We characterized the electroresponsive and morphological properties of neurons in the bed nucleus of the stria terminalis (BNST). Previously, Rainnie and colleagues distinguished three cell types in the anterolateral region of BNST (BNST-AL): low-threshold bursting cells (LTB; type II) and regular spiking neurons that display time-dependent (RS; type I) or fast (fIR; type III) inward rectification in the hyperpolarizing direction (Hammack SE, Mania I, Rainnie DG. J Neurophysiol 98: 638 -56, 2007). We report that the same neuronal types exist in the anteromedial (AM) and anteroventral (AV) regions of BNST. In addition, we observed two hitherto unreported cell types: late-firing (LF) cells, only seen in BNST-AL, that display a conspicuous delay to firing, and spontaneously active (SA) neurons, only present in BNST-AV, firing continuously at rest. However, the feature that most clearly distinguished the three BNST regions was the incidence of LTB cells (approximately 40 -70%) and the strength of their bursting behavior (both higher in BNST-AM and AV relative to AL). The incidence of RS cells was similar in the three regions (ϳ25%), whereas that of fIR cells was higher in BNST-AL (ϳ25%) than AV or AM (Յ8%). With the use of biocytin, two dominant morphological cell classes were identified but they were not consistently related to particular physiological phenotypes. One neuronal class had highly branched and spiny dendrites; the second had longer but poorly branched and sparsely spiny dendrites. Both often exhibited dendritic varicosities. Since LTB cells prevail in BNST, it will be important to determine what inputs set their firing mode (tonic vs. bursting) and in what behavioral states.bed nucleus of the stria terminalis; anxiety; fear; intrinsic properties; morphology DESPITE ANATOMICAL SIMILARITIES (Alheid and Heimer 1988; deOlmos and Heimer 1999;McDonald 2003), dense interconnections (Krettek and Price 1978a,b; Dong et al. 2001a), and functional kinship (Walker et al. 2003) between the amygdala and bed nucleus of the stria terminalis (BNST), there is a stark contrast between our understanding of these two structures. For instance, numerous in vitro studies have examined the physiological properties of amygdala neurons, mechanisms of synaptic transmission, neuromodulation, and activity-dependent plasticity (reviewed in Sah et al. 2003;Pape and Pare 2010). In contrast, relatively few reports on these themes are available for the BNST (reviewed in McElligott and Winder 2009; Hammack et al. 2009). As a result, the operations carried out by the BNST remain poorly understood.
Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome. Lewis rats were subjected to classical auditory fear conditioning before or after exposure to a predatory threat that mimics a type of traumatic stress that leads to PTSD in humans. Exploratory behavior on the elevated plus maze 1 wk after predatory threat exposure was used to distinguish resilient vs. PTSD-like rats. Properties of extinction varied depending on whether fear conditioning and extinction occurred before or after predatory threat. When fear conditioning was carried out after predatory threat, PTSD-like rats showed a marked extinction deficit compared with resilient rats. In contrast, no differences were seen between resilient and PTSD-like rats when fear conditioning and extinction occurred prior to predatory threat. These findings in Lewis rats closely match the results seen in humans with PTSD, thereby suggesting that studies comparing neuronal interactions in resilient vs. at-risk Lewis rats might shed light on the causes and pathophysiology of human PTSD.
Turesson HK, Rodríguez-Sierra OE, Pare D. Intrinsic connections in the anterior part of the bed nucleus of the stria terminalis. J Neurophysiol 109: 2438 -2450, 2013. First published February 27, 2013 doi:10.1152/jn.00004.2013.-Intrinsic connections in the anterior portion of the bed nucleus of the stria terminalis (BNST-A) were studied using patch recordings and ultraviolet (UV) glutamate uncaging (GU) in vitro. UV light was delivered at small BNST-A sites in a grid-like pattern while evoked responses were monitored in different BNST-A regions. Three sectors were distinguished in the BNST-A using fiber bundles readily identifiable in transilluminated slices: the anterior commissure, dividing the BNST-A into dorsal and ventral (BNST-AV) regions, and the intra-BNST component of the stria terminalis, subdividing the dorsal portion into medial (BNST-AM) and lateral (BNST-AL) regions. Overall, GU elicited GABAergic inhibitory postsynaptic potentials (IPSPs) more frequently than excitatory postsynaptic potentials. The incidence of intraregional connections was higher than interregional links. With respect to the latter, asymmetric connections were seen between different parts of the BNST-A. Indeed, while reciprocal connections were found between the BNST-AL and BNST-AM, BNST-AL to BNST-AM connections were more frequent than in the opposite direction. Similarly, while GU in the BNST-AM or BNST-AL often elicited IPSPs in BNST-AV cells, the opposite was rarely seen. Within the BNST-AM, connections were polarized, with dorsal GU sites eliciting IPSPs in more ventrally located cells more frequently than the opposite. This trend was not seen in other regions of the BNST. Consistent with this, most BNST-AM cells had dorsally directed dendrites and ventrally ramified axons, whereas this morphological polarization was not seen in other parts of the BNST-A. Overall, our results reveal a hitherto unsuspected level of asymmetry in the connections within and between different BNST-A regions, implying a degree of interdependence in their activity.
Vibrissae-related sensorimotor cortex controls whisking movements indirectly via modulation of lower-level sensorimotor loops and a brainstem central pattern generator (CPG). Two different whisker representations in primary motor cortex (vM1) affect whisker movements in different ways. Prolonged microstimulation in RF, a larger anterior subregion of vM1, gives rise to complex face movements and whisker retraction while the same stimulation evokes large-amplitude rhythmic whisker movement in a small caudo-medial area (RW). To characterize the motor cortex representation of explorative whisking movements, here we recorded RW units in head-fixed rats trained to contact a moving object with one whisker. RW single units were found to encode two aspects of whisker movement independently, albeit on slow time scales (hundreds of milliseconds). The first is whisker position. The second consists of speed (absolute velocity), intensity (instantaneous power), and frequency (spectral centroid). The coding for the latter three parameters was tightly correlated and realized by a continuum of RW responses-ranging from a preference of movement to a preference of rest. Information theory analysis indicated that RW spikes carry most information about position and frequency, while intensity and speed are less well represented. Further, investigating multiple and single RW units, we found a lack of phase locking, movement anticipation, and contactrelated tactile responses. These findings suggest that RW neither programs detailed whisker trajectories nor initiates them. Nor does it play a role in processing object touch. Its relationship to whisking is thus indirect and may be related to movement monitoring, perhaps using feedback from the CPG.
A highly conserved network of brain structures regulates the expression of fear and anxiety in mammals. Many of these structures display abnormal activity levels in post-traumatic stress disorder (PTSD). However, some of them, like the bed nucleus of the stria terminalis (BNST) and amygdala, are comprised of several small sub-regions or nuclei that cannot be resolved with human neuroimaging techniques. Therefore, we used a well-characterized rat model of PTSD to compare neuronal properties in resilient vs PTSD-like rats using patch recordings obtained from different BNST and amygdala regions in vitro. In this model, a persistent state of extreme anxiety is induced in a subset of susceptible rats following predatory threat. Previous animal studies have revealed that the central amygdala (CeA) and BNST are differentially involved in the genesis of fear and anxiety-like states, respectively. Consistent with these earlier findings, we found that between resilient and PTSD-like rats were marked differences in the synaptic responsiveness of neurons in different sectors of BNST and CeA, but whose polarity was region specific. In light of prior data about the role of these regions, our results suggest that control of fear/anxiety expression is altered in PTSD-like rats such that the influence of CeA is minimized whereas that of BNST is enhanced. A model of the amygdalo-BNST interactions supporting the PTSD-like state is proposed.
Abstract. Research studies that investigate the differences between "female" and "male" brain implicitly try to naturalize these categories that not only have biological components but also social and cultural components. It has been shown that scientific journals and media have a tendency to report more frequently those studies that confirm the binary interpretation of sex/gender as something dimorphic, fixed, and static. Nonetheless, when evidences are considered altogether, several inconsistencies are revealed and no major differences between the sexes/genders remained. Hence, the public debate should question those categories that we assume as natural in order to avoid essentialist and deterministic positions.Keywords. Sex; gender; brain; binary model; media.*Contato: olgars@neuro.ufrn.br IntroduçãoA presença de informações neurocientíficas nos meios de comunicação aumentou enormemente na última década. Uma análise de Connor et al (2012) mostra que de 2000 a 2010 dobrou o número de artigos sobre temas de neurociên-cia na imprensa. Os autores identificaram três eixos temáti-cos principais: o cérebro como um capital para ser otimizado e / ou explorado, o cérebro como um indício de diferença para validar categorias impostas sobre as pessoas, e o cérebro como uma prova biológica para validar algum fenômeno ou crença. No presente artigo, pretende-se particularmente analisar uma situação em que a neurociência é utilizada como "indício de diferença" para validar que existem diferenças essenciais ou naturais entre homens e mulheres. Se é certo que exista um dimorfismo sexual associado à reprodução, é inválido inferir que esse dimorfismo desemboque -de forma nítida -na diferenciação entre um cérebro "masculino" e um "feminino", da qual surjam características dicotômicas em termos de personalidade, cognição, emoção e comportamento. Como veremos adiante, não se pode responsabilizar apenas a mídia por querer validar este "indício de diferença"; a própria ciência, ao formular suas hipóteses, projetar os experimentos e interpretar os resultados, contribui para essa validação. Assim, uma das premissas deste ensaio é que os cientistas não obtêm "verdades objetivas" e livres de vieses quando relatam os resultados de suas pesquisas. Pelo contrá-rio, estas "verdades" se inferem de interpretações que podem ser influenciadas pelo entorno social e cultural -por mais que estejam baseadas em resultados da experimentação. Desta maneira, o fluxo de informações entre cientistas e sociedade não ocorre de forma unidirecional, mas sim bidirecional. Consequentemente, para entender como a mídia transmite os conteúdos científicos à sociedade, também devemos analisar como as crenças e valores da sociedade estão entrelaçadas com o trabalho científico.No nosso caso particular, seria simplista nos apoiarmos apenas na análise retórica do conteúdo nos meios de comunicação, uma vez que não se pretende sugerir que estes sejam a única fonte incitadora deste indício de diferença entre homens e mulheres. Pelo contrário, nas ciências naturais e comport...
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