A distinct parabrachial–to–lateral hypothalamus circuit for motivational suppression of feeding by nociception

The motivation to eat is not only shaped by nutrition but also competed by external stimuli including pain. How the mouse hypothalamus, the feeding regulation center, integrates nociceptive inputs to modulate feeding is unclear. Within the key nociception relay center parabrachial nucleus (PBN), we demonstrated that neurons projecting to the lateral hypothalamus (LHPBN) are nociceptive yet distinct from danger-encoding central amygdala–projecting (CeAPBN) neurons. Activation of LHPBN strongly suppressed feeding by limiting eating frequency and also reduced motivation to work for food reward. Refined approach-avoidance paradigm revealed that suppression of LHPBN, but not CeAPBN, sustained motivation to obtain food. The effect of LHPBN neurons on feeding was reversed by suppressing downstream LHVGluT2 neurons. Thus, distinct from a circuit for fear and escape responses, LHPBN neurons channel nociceptive signals to LHVGluT2 neurons to suppress motivational drive for feeding. Our study provides a new perspective in understanding feeding regulation by external competing stimuli.

When two worlds collide: the influence of an obstacle in peripersonal space on multisensory encoding

Multisensory coding of the space surrounding our body, the peripersonal space, is crucial for motor control. Recently, it has been proposed that an important function of multisensory coding is that it allows anticipation of the tactile consequences of contact with a nearby object. Indeed, performing goal-directed actions (i.e. pointing and grasping) induces a continuous visuotactile remapping as a function of on-line sensorimotor requirements. Here, we investigated whether visuotactile remapping can be induced by obstacles, e.g. objects that are not the target of the grasping movement. In the current experiment, we used a cross-modal obstacle avoidance paradigm, in which participants reached past an obstacle to grasp a second object. Participants indicated the location of tactile targets delivered to the hand during the grasping movement, while a visual cue was sometimes presented simultaneously on the to-be-avoided object. The tactile and visual stimulation was triggered when the reaching hand passed a position that was drawn randomly from a continuous set of predetermined locations (between 0 and 200 mm depth at 5 mm intervals). We observed differences in visuotactile interaction during obstacle avoidance dependent on the location of the stimulation trigger: visual interference was enhanced for tactile stimulation that occurred when the hand was near the to-be-avoided object. We show that to-be-avoided obstacles, which are relevant for action but are not to-be-interacted with (as the terminus of an action), automatically evoke the tactile consequences of interaction. This shows that visuotactile remapping extends to obstacle avoidance and that this process is flexible.

Aversion to Desflurane and Isoflurane in Sprague-Dawley Rats (Rattus norvegicus)

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an aversion-avoidance paradigm, 24 rats were exposed to isoflurane or desflurane (n = 12 per group) at initial exposure. Fourteen rats were then re-exposed to isoflurane or desflurane (n = 7 per group), after a 7 days washout period. Initial exposure: time to recumbency was faster for desflurane than isoflurane (p = 0.0008, 95% CI [-12.9 to 32.6 s]), with 9/12 and 6/12 rats becoming recumbent, respectively. At initial exposure, there was no difference between groups in time to withdrawal (p = 0.714). At re-exposure, all rats withdrew and no rats became recumbent. Time to withdrawal at re-exposure did not differ between treatment groups (p = 0.083). Compared to initial exposure, time to withdrawal during re-exposure was similar for isoflurane (p = 0.228) and faster with desflurane (p = 0.012, 95% CI [19.1 to 49.5 s]). Isoflurane and desflurane are similarly aversive, with aversion increasing at re-exposure. The shorter time from exposure to recumbency with desflurane indicates that any distress is of a shorter duration when compared with isoflurane.

Pharmacological Approach of Pistacia Vera Fruit to Assess Learning and Memory Potential in Chemically-Induced Memory Impairment in Mice

Objective: The present study was designed to investigate the potential of Pistacia vera (P. vera) fruits in experimental memory impairments in mice. Material & Methods: Memory impairment was induced in Swiss Albino mice by scopolamine (0.4mg mg/kg. i.p). Animals were divided into five separate groups of six animals each, positive control group received carboxy methyl cellulose (CMC) as vehicle, negative control group received scopolamine with vehicle, and standard group received donepezil (5mg/kg i.p) with Scopolamine. Ethanolic extract of P. vera (EEPV) at doses of 200mg/kg & 400mg/kg p.o were administered to group test1 & test 2 respectively along with scopolamine. Elevated plus maze (EPM), passive avoidance paradigms and morris water maze (MWM) were used as exteroceptive behavioral models to access learning and memory activity. Transfer latency, step down latency and escape latency parameters were evaluated plus maze, passive avoidance paradigm, morris water maze. Thereafter lipid peroxidation test, glutathione level and catalase activities were estimated in homogenized brain of mice. Results: Pretreatment of mice with EEPV (200mg/kg & 400mg/kg) significantly reduced scopolamine induced amnesia. The obtained data clearly revealed that there was increase in escape latency in MWM and also increase in step down latency in passive avoidance paradigm. Transfer latencey was found to be decrease in EPM and biochemical. Parameters were clearly satisfied the data as compared to negative control group which was indicative of cognitive improvement. Conclusion: P. vera fruit extract demonstrated to improve cognitive process by enhancing memory in different experimental paradigm such as EPM, passive avoidance and MWM when administered orally. Hence it would be worthwhile to explore the potential of this plant in the management of memory disorders.

Zebrafish use visual cues and geometric relationships to form a spatial memory

Animals use salient cues to navigate in their environment, but their specific cognitive strategies are largely unknown. We developed a conditioned place avoidance paradigm to discover whether and how zebrafish form spatial memories in a Y-shaped maze. Juvenile zebrafish, older than three weeks, learned to avoid the arm of the maze that was cued with a mild electric shock. We found that the fish required distinct visual patterns to develop a conditioned response. Interestingly, individual fish solve this task in different ways: by staying in the safe center of the maze, by preference for one, or both, of the safe patterns, or by mixed strategies. In experiments in which the learned patterns were swapped, rotated or replaced, the animals could transfer the association of safety to a different arm or to a different pattern using either visual cues or location as the conditioned stimulus. These findings show that juvenile zebrafish exhibit several complementary spatial learning modes and pave the way for neurobiological studies of navigational mechanisms in this model species.

Valence and Intensity of Video Stimuli of Dogs and Conspecifics in Sheep: Approach-Avoidance, Operant Response, and Attention

Stimuli are often presumed to be either negative or positive. However, animals’ judgement of their negativity or positivity cannot generally be assumed. A possibility to assess emotional states in animals elicited by stimuli is to investigate animal preferences and their motivation to gain access to these stimuli. This study’s aim was to assess the valence of social stimuli in sheep. We used silent videos of varying intensity of dogs as negative versus conspecifics as positive stimuli in three approaches: (1) an approach–avoidance paradigm; (2) operant conditioning using the video stimuli as reinforcers; and (3) an attention test. In the latter, we assessed differential attention of sheep to simultaneous projections by automatically tracking sheep head and ear postures and recording brain activity. With these approaches, it was difficult to support that the sheep’s reactions varied according to the stimuli’s presumed valence and intensity. The approach–avoidance paradigm and attention test did not support the assumption that dog videos were more negative than sheep videos, though sheep reacted to the stimuli presented. Results from the operant conditioning indicated that sheep were more prone to avoid videos of moving dogs. Overall, we found that standard video images may not be ideal to represent valence characteristics of stimuli to sheep.