Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic cortex (PL) respond to both threat-and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals’ decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock and food-paired cues, we observed two distinct phenotypes during conflict: I) rats that continued to press a lever for food (Pressers); and ii) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated foodseeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision making by regulating threat-avoidance vs. reward-approach behaviors.Fil: Fernandez Leon, Jose Alberto. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. University of Texas Health Science Center at Houston; Estados UnidosFil: Engelke, Douglas S.. University of Texas Health Science Center at Houston; Estados UnidosFil: Aquino Miranda, Guillermo. University of Texas Health Science Center at Houston; Estados UnidosFil: Goodson, Alexandria. University of Texas Health Science Center at Houston; Estados Unidos. Rice University; Estados UnidosFil: Rasheed, María N.. University of Texas Health Science Center at Houston; Estados UnidosFil: Do Monte, Fabricio H.. University of Texas Health Science Center at Houston; Estados Unidos. Rice University; Estados Unido

Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats

<p>Abstract</p> <p>Background</p> <p>Inflammatory responses in brain are primarily mediated by microglia, but growing evidence suggests a crucial importance of astrocytes. S100B, a calcium-binding protein secreted by astrocytes, has properties of a neurotrophic or an inflammatory cytokine. However, it is not known whether primary signals occurring during induction of an inflammatory response (e.g. lipopolysaccharide, LPS) directly modulate S100B.</p> <p>Methods</p> <p>In this work, we evaluated whether S100B levels in cerebrospinal fluid (CSF) and serum of Wistar rats are affected by LPS administered by intraperitoneal (IP) or intracerebroventricular (ICV) injection, as well as whether primary astrocyte cultures respond directly to lipopolysaccharide.</p> <p>Results</p> <p>Our data suggest that S100B secretion in brain tissue is stimulated rapidly and persistently (for at least 24 h) by ICV LPS administration. This increase in CSF S100B was transient when LPS was IP administered. In contrast to these S100B results, we observed an increase in in TNFα levels in serum, but not in CSF, after IP administration of LPS. In isolated astrocytes and in acute hippocampal slices, we observed a direct stimulation of S100B secretion by LPS at a concentration of 10 μg/mL. An involvement of TLR4 was confirmed by use of specific inhibitors. However, lower levels of LPS in astrocyte cultures were able to induce a decrease in S100B secretion after 24 h, without significant change in intracellular content of S100B. In addition, after 24 h exposure to LPS, we observed a decrease in astrocytic glutathione and an increase in astrocytic glial fibrillary acidic protein.</p> <p>Conclusions</p> <p>Together, these data contribute to the understanding of the effects of LPS on astrocytes, particularly on S100B secretion, and help us to interpret cerebrospinal fluid and serum changes for this protein in neuroinflammatory diseases. Moreover, non-brain S100B-expressing tissues may be differentially regulated, since LPS administration did not lead to increased serum levels of S100B.</p

Hiding Relations

The present vogue of ‘managing for development results’ is an expression of a historically dominant mode of thought in international aid – ‘substantialism’ – which sees the world primarily in terms of ‘entities’ such as ‘poverty’, ‘basic needs’, ‘rights’, ‘women’, or ‘results’. Another important mode of thought, ‘relationalism’ – in association more generally with ideas of process and complexity – appears to be absent in the thinking of aid institutions. Drawing on my own experiences of working with the UK Department for International Development (DFID), I illustrate how despite formally subscribing to the institution’s substantialist view of the world, some staff are ‘closet relationists’, behaving according to one mode of thought while officially framing their action in terms of the other, more orthodox mode. In so doing, they may be unwittingly keeping international aid sufficiently viable - by the apparent proof of the efficacy of results-based management - to enable the institution as a whole to maintain its substantialist imaginary

Temporal and Behavioral Variability in Cannabinoid Receptor Expression in Outbred Mice Submitted to Ethanol-Induced Locomotor Sensitization Paradigm

Background There is a close relationship between the endocannabinoid system and alcoholism. This study investigated possible differential expression of cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) in an outbred mice strain displaying behavioral variability to ethanol (EtOH)-induced locomotor sensitization.Methods Male adult Swiss mice treated chronically with EtOH (2g/kg, i.p., daily for 21days) were classified as EtOH_High or EtOH_Low according to their locomotor activity after the 21st EtOH injection. A control group was similarly injected with saline. Temporal analysis of CB1R and CB2R immunoreactivity was performed in 3 different occasions: (i) at the end of chronic EtOH treatment, (ii) on the fifth day of EtOH withdrawal, and (iii) after EtOH challenge.Results Overall, no differences were seen between experimental groups regarding the CB1R at the end of acquisition. However, there were decreases in CB2R in the prefrontal cortex and the hippocampus in EtOH_Low mice. On the fifth day of withdrawal, only EtOH_High mice presented increase in CB1R. Nonetheless, CB2R up-regulation was observed in both EtOH_High and EtOH_Low mice. EtOH challenge counteracted CB1R and CBR2 up-regulation, mainly in the EtOH_High, in structures related to emotionality, such as prefrontal cortex, ventral tegmental area, amygdala, striatum, and hippocampus.Conclusions There are different patterns of cannabinoid receptor expression during locomotor sensitization paradigm, at both temporal and behavioral perspectives. We hypothesize that CB2R down-regulation might be related to resilience to develop locomotor sensitization, while CB1R up-regulation relates to withdrawal aspects in sensitized mice.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Neurobiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat & Med Psychol, São Paulo, BrazilFac Ciencias Med Santa Casa, Dept Physiol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat & Med Psychol, São Paulo, BrazilFAPESP: 2011/03184-0FAPESP: 2009/16305-0FAPESP: 2009/16307-2Web of Scienc