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Serotonin modulates diverse phenotypes and functions including depressive, aggressive, impulsive, and feeding behaviors, all of which have reward-related components. To date, research has focused on understanding these effects by measuring and manipulating dorsal raphe serotonin neurons and using single-receptor approaches. These studies have led to a better understanding of the heterogeneity of serotonin actions on behavior; however, they leave open many questions about the timing and location of serotonin's actions modulating the neural circuits that drive these behaviors. Recent advances in genetically encoded fluorescent biosensors, including the GPCR activation-based sensor for serotonin (GRAB-5-HT), enable the measurement of serotonin release in mice on a timescale compatible with a single rewarding event without corelease confounds. Given substantial evidence from slice electrophysiology experiments showing that serotonin influences neural activity of the striatal circuitry, and the known role of the dorsal medial striatal (DMS) in reward-directed behavior, we focused on understanding the parameters and timing that govern serotonin release in the DMS in the context of reward consumption, external reward value, internal state, and cued reward. Overall, we found that serotonin release is associated with each of these and encodes reward anticipation, value, approach, and consumption in the DMS. [ABSTRACT FROM AUTHOR]

As central nervous system residents, mast cells contain many cytokines and are localized primarily near large blood vessels in the diencephalon and within the leptomeninges, making them candidates for immune to neural 'cross talk.' Using mast cell-deficient [Kit.sup.W-sh/W-sh] mice, we assessed the role of these cells in the thermoregulatory component of the immune response to lipopolysaccharide (LPS). [Kit.sup.W-sh/W-sh and wild-type (WT) mice differed in several respects in response to injection of a high dose of LPS (1 mg/kg ip). Core temperature ([T.sub.c]) of WT mice decreased by ~3[degrees]C, whereas [Kit.sup.W-sh/W-sh] mice did not become hypothermic but instead exhibited pronounced low-frequency [T.sub.c] oscillations around their baseline temperature. In addition, [Kit.sup.W-sh/W-sh] mice had lower levels of whole brain TNF-[alpha] but no differences in IL-1[beta], IL-6, IFN-[gamma] or histamine compared with WT mice following injection of the high dose of LPS, consistent with the role of TNF-[alpha] in sepsis. [Kit.sup.W-sh/W-sh] mice had increased resistance to LPS, and some survived a dose of LPS that was lethal in littermate controls. In contrast, [Kit.sup.W-sh/W-sh] and WT mice were similar in other aspects, namely, in the hyperthermia following injection of TNF-[alpha] (1.5 [micro]g icv), reduced nighttime [T.sub.c] and locomotor activity (to 1 mg/kg LPS), response to a low dose of LPS (10 [micro]g/kg ip), and response to subcutaneous turpentine injection. These results indicate that mast cells play a role in the regulation of thermoregulatory responses and survival following sepsis induction and suggest a brain site of action. tumor necrosis factor-[alpha]; interleukins; interferon-[gamma]; histamine; mast cell-deficient sash mice; hypothermia

Hypothalamic neurons are regarded as essential for integrating thermal afferent information from skin and core and issuing commands to autonomic and behavioral effectors that maintain core temperature ([T.sub.c]) during cold exposure and for the control of energy expenditure more generally. Caudal brain stem neurons are necessary elements of the hypothalamic effector pathway and also are directly driven by skin and brain cooling. To assess whether caudal brain stem processing of thermal afferent signals is sufficient to drive endemic effectors for thermogenesis, heart rate (HR), [T.sub.c], and activity responses of chronic decerebrate (CD) and control rats adapted to 23[degrees]C were compared during cold exposure (4, 8, or 12[degrees]C) for 6 h. Other CDs and controls were exposed to 4 or 23[degrees]C for 2 h, and tissues were processed for norepinephrine turnover (NETO), a neurochemical measure of sympathetic drive. Controls maintained [T.sub.c] for all temperatures. CDs maintained [T.sub.c] for the 8 and 12[degrees]C exposures, but [T.sub.c] declined 2[degrees]C during the 4[degrees]C exposure. Cold exposure elevated HR in CDs and controls alike. Tachycardia magnitude correlated with decreases in environmental temperature for controls, but not CDs. Cold increased NETO in brown adipose tissue, heart, and some white adipose tissue pads in CDs and controls compared with their respective room temperature controls. These data demonstrate that, in neural isolation from the hypothalamus, cold exposure drives caudal brain stem neuronal activity and engages local effectors that trigger sympathetic energetic and cardiac responses that are comparable in many, but not in all, respects to those seen in neurologically intact rats. energy balance; thermoregulation; anterior hypothalamus; heart rate; body temperature; sympathetic drive; norepinephrine turnover; white adipose tissue; brown adipose tissue

Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/ aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1). However, no previous studies have investigated EAAT3 in basal ganglia circuits or in relation to OCD-related behavior. Here, we report a model of Slc1a1 loss based on an excisable STOP cassette that yields successful ablation of EAAT3 expression and function. Using amphetamine as a probe, we found that EAAT3 loss prevents expected increases in (i) locomotor activity, (ii) stereotypy, and (iii) immediate early gene induction in the dorsal striatum following amphetamine administration. Further, Slc1a1-STOP mice showed diminished grooming in an SKF-38393 challenge experiment, a pharmacologic model of OCDlike grooming behavior. This reduced grooming is accompanied by reduced dopamine D1 receptor binding in the dorsal striatum of Slc1a1-STOP mice. Slc1a1-STOP mice also exhibit reduced extracellular dopamine concentrations in the dorsal striatum both at baseline and following amphetamine challenge. Viral-mediated restoration of Slc1a1/EAAT3 expression in the midbrain but not in the striatum results in partial rescue of amphetamine-induced locomotion and stereotypy in Slc1a1-STOP mice, consistent with an impact of EAAT3 loss on presynaptic dopaminergic function. Collectively, these findings indicate that the most consistently associated OCD candidate gene impacts basal ganglia-dependent repetitive behaviors. [ABSTRACT FROM AUTHOR]