High-Energy-Density Material with Magnetically Modulated Ignition.

Preparation of a redox-frustrated high-energy-density energetic material is achieved by gentle protolysis of Mn[N(SiMe3)2]2 with the perchlorate salt of the tetrazolamide [H2NtBuMeTz]ClO4 (Tz = tetrazole), yielding the Mn6N6 hexagonal prismatic cluster, Mn6(µ3-NTztBuMe)6(ClO4)6. Quantum mechanics-based molecular dynamics simulations of the decomposition of this molecule predict that magnetic ordering of the d5 Mn2+ ions influences the pathway and rates of decomposition, suggesting that the initiation of decomposition of the bulk material might be significantly retarded by an applied magnetic field. We report here experimental tests of the prediction showing that the presence of a 0.5 T magnetic field modulates the ignition onset temperature by +10.4 ± 3.9 °C (from 414 ± 4 °C), demonstrating the first example of a magnetically modulated explosive.

Sex differences in circuits activated by corticotropin releasing factor in rats.

Women are more likely than men to suffer from psychiatric disorders characterized by corticotropin releasing factor (CRF) hypersecretion, suggesting sex differences in CRF sensitivity. In rodents, sex differences in the sensitivity of specific brain regions to CRF have been identified. However, regions do not work in isolation, but rather form circuits to coordinate distinct responses to stressful events. Here we examined whether CRF activates different circuits in male and female rats. Following central administration of CRF or artificial cerebrospinal fluid (aCSF), neuronal activation in stress-related areas was assessed using cFOS. Functional connectivity was gauged by correlating the number of cFOS-positive cells between regions and then identifying differences within each sex in correlations for aCSF-treated and CRF-treated groups. This analysis revealed that CRF altered different circuits in males and females. As an example, CRF altered correlations involving the dorsal raphe in males and the bed nucleus of the stria terminalis in females, suggesting sex differences in stress-activated circuits controlling mood and anxiety. Next, plasma estradiol and progesterone levels were correlated with cFOS counts in females. Negative correlations between estradiol and neuronal activation in the regions within the extended amygdala were found in CRF-treated, but not aCSF-treated females. This result suggests that estrogens and CRF together modulate the fear and anxiety responses mediated by these regions. Collectively, these studies reveal sex differences in the way brain regions work together in response to CRF. These differences could drive different stress coping strategies in males and females, perhaps contributing to sex biases in psychopathology.

Touchscreen Sustained Attention Task (SAT) for Rats.

Sustained attention is the ability to monitor intermittent and unpredictable events over a prolonged period of time. This attentional process subserves other aspects of cognition and is disrupted in certain neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Thus, it is clinically important to identify mechanisms that impair and improve sustained attention. Such mechanisms are often first discovered using rodent models. Therefore, several behavior procedures for testing aspects of sustained attention have been developed for rodents. One, first described by McGaughy and Sarter (1995), called the sustained attention task (SAT), trains rats to distinguish between signal (i.e., brief light presentation) and non-signal trials. The signals are short and thus require careful attention to be perceived. Attentional demands can be increased further by introducing a distractor (e.g., flashing houselight). We have modified this task for touchscreen operant chambers, which are configured with a touchscreen on one wall that can present stimuli and record responses. Here we detail our protocol for SAT in touchscreen chambers. Additionally, we present standard measures of performance in male and female Sprague-Dawley rats. Comparable performance on this task in both sexes highlights its use for attention studies, especially as more researchers are including female rodents in their experimental design. Moreover, the easy implementation of SAT for the increasingly popular touchscreen chambers increases its utility.

Method for testing sustained attention in touchscreen operant chambers in rats.

BACKGROUND: Sustained attention, the ability to detect rare and unpredictable events, is central to cognitive performance. This construct can be tested in rodents using a Sustained Attention Task (SAT), where rats are trained to detect an unpredictably occurring signal (a brief light presentation) from non-signal events. The traditional version of this task utilizes an operant chamber with a central panel light for the signal and two retractable response levers. Adaptation of SAT to the increasingly popular touchscreen operant chambers, which do not have levers or fixed lights, could enhance the versatility of the task. NEW METHOD: Here we developed a touchscreen version of SAT where the light signal is presented in the center of the touchscreen, followed by a tone to indicate the beginning of the response period. Rats indicate their choice during this period by touching their nose to one of two touchscreen response areas. The remaining parameters were kept similar to the traditional version. RESULTS: Rats acquired touchscreen SAT at a similar rate to the traditional version. As with the traditional version, shorter stimulus durations on the signaled trials reduced accuracy and the presence of a distractor (a flashing houselight) disrupted performance on the touchscreen version. COMPARISON TO EXISTING METHOD: Collectively, these data suggest that the touchscreen version is comparable to the traditional version of the SAT, and is an equally valid way of measuring sustained attention. CONCLUSIONS: Many researchers with touchscreen chambers could easily implement our modifications in order to study sustained attention.

Sex differences in corticotropin releasing factor-evoked behavior and activated networks.

Hypersecretion of corticotropin releasing factor (CRF) is linked to the pathophysiology of major depression and post-traumatic stress disorder, disorders that are more common in women than men. Notably, preclinical studies have identified sex differences in CRF receptors that can increase neuronal sensitivity to CRF in female compared to male rodents. These cellular sex differences suggest that CRF may regulate brain circuits and behavior differently in males and females. To test this idea, we first evaluated whether there were sex differences in anxiety-related behaviors induced by the central infusion of CRF. High doses of CRF increased self-grooming more in female than in male rats, and the magnitude of this effect in females was greater when they were in the proestrous phase of their estrous cycle (higher ovarian hormones) compared to the diestrous phase (lower ovarian hormones), which suggests that ovarian hormones potentiate this anxiogenic effect of CRF. Brain regions associated with CRF-evoked self-grooming were identified by correlating a marker of neuronal activation, cFOS, with time spent grooming. In the infralimbic region, which is implicated in regulating anxiety, the correlation for CRF-induced neuronal activation and grooming was positive in proestrous females, but negative for males and diestrous females, indicating that ovarian hormones altered this relationship between neuronal activation and behavior. Because CRF regulates a number of regions that work together to coordinate different aspects of responding to stress, we then examined more broadly whether CRF-activated functional connectivity networks differed between males and cycling females. Interestingly, hormonal status altered correlations for CRF-induced neuronal activation between a variety of brain regions, but the most striking differences were found when comparing proestrous females to males, particularly when comparing neuronal activation between prefrontal cortical and other forebrain regions. These results suggest that ovarian hormones alter the way brain regions work together in response to CRF, which could drive different strategies for coping with stress in males versus females. These sex differences in stress responses could also help explain female vulnerability to psychiatric disorders characterized by CRF hypersecretion.

Trace conditioning and the hippocampus: the importance of contiguity.

Trace conditioning, a form of classical conditioning in which the presentation of the conditioned stimulus (CS) and the unconditioned stimulus (US) is separated in time by an interstimulus interval, requires an intact hippocampus. In contrast, classical conditioning procedures in which the CS and US are not separated by an interstimulus interval (i.e., delay conditioning procedures) typically do not (Solomon et al., 1986). However, why trace conditioning is dependent on the hippocampus is unknown. Several theories suggest that it is specifically the discontiguity between the CS and US in trace conditioning that critically engages the hippocampus. However, there are other explanations that do not depend on discontiguity. To determine whether the lack of contiguity renders trace conditioning hippocampal dependent, we designed a "contiguous trace conditioning" (CTC) paradigm in which CS-US contiguity is restored by re-presenting the CS simultaneously with the US. Although rats with excitotoxic lesions of the hippocampus could not learn a standard trace fear-conditioning paradigm, lesioned rats trained on CTC showed significant conditioning, at levels similar to those with sham surgeries. Importantly, lesioned rats trained solely with simultaneous CS-US presentations did not demonstrate conditioning. Together, these data suggest that rats with hippocampal lesions can form a memory of a trace CS-US association when contiguity is restored. Therefore, the dependence of traditional trace paradigms on the hippocampus can be attributed to the absence of temporal contiguity.