Chronic hyperpalatable diet induces impairment of hippocampal-dependent memories and alters glutamatergic and fractalkine axis signaling.

Chronic consumption of hyperpalatable and hypercaloric foods has been pointed out as a factor associated with cognitive decline and memory impairment in obesity. In this context, the integration between peripheral and central inflammation may play a significant role in the negative effects of an obesogenic environment on memory. However, little is known about how obesity-related peripheral inflammation affects specific neurotransmission systems involved with memory regulation. Here, we test the hypothesis that chronic exposure to a highly palatable diet may cause neuroinflammation, glutamatergic dysfunction, and memory impairment. For that, we exposed C57BL/6J mice to a high sugar and butter diet (HSB) for 12 weeks, and we investigated its effects on behavior, glial reactivity, blood-brain barrier permeability, pro-inflammatory features, glutamatergic alterations, plasticity, and fractalkine-CX3CR1 axis. Our results revealed that HSB diet induced a decrease in memory reconsolidation and extinction, as well as an increase in hippocampal glutamate levels. Although our data indicated a peripheral pro-inflammatory profile, we did not observe hippocampal neuroinflammatory features. Furthermore, we also observed that the HSB diet increased hippocampal fractalkine levels, a key chemokine associated with neuroprotection and inflammatory regulation. Then, we hypothesized that the elevation on glutamate levels may saturate synaptic communication, partially limiting plasticity, whereas fractalkine levels increase as a strategy to decrease glutamatergic damage.

On the effect of social cue valence in contextual memory persistence.

Social cues are valuable sensorial stimuli to the acquisition and retrieval of contextual memories. Here, we asked whether the valence of social cues would impact the formation of contextual memories. Adult male C57/BL6 mice were exposed to either conditioned place preference (CPP) or avoidance (CPA). As positive stimuli we used social interaction with a female (IF), while interaction with a male CD1 mice (IM) was used as negative stimulus. Contextual memory was tested 24 h and 7 days after conditioning. Aggressive behavior of CD1, as well as interaction with the female were quantified along the conditioning sessions. IM, but not IF, was salient enough to induce contextual memory estimated by the difference between the time in the conditioned context during test and habituation. Next, we chose two odors with innate behavioral responses and opposite valence to narrow down the sociability to one of its sensorial sources of information - the olfaction. We used urine from females in proestrus (U) and 2,4,5-trimethyl thiazoline (TMT), a predator odor. TMT decreased and U increased the time in the conditioned context during the test performed 24 h and 7 days after conditioning. Taken together, our results suggest that contextual memories conditioned to social encounters are difficult to stablish in mice, specially the one with positive valence. On the other hand, using odors with ecological relevance is a promising strategy to study long-term contextual memories with opposite valences. Ultimately, the behavioral protocol proposed here offers the advantage of studying contextual memories with opposite valences using unconditioned stimulus from the same sensorial category such as olfaction.

Early postnatal l-Dopa treatment causes behavioral alterations in female vs. male young adult Swiss mice.

Dopaminergic signaling and neurodevelopment alterations are associated with several neuropsychiatric disorders. Knockout mice for dopamine transporters (DAT) as well as site-specific knockout mice lacking dopaminergic D2 autoreceptors in dopaminergic neurons (DA-D2RKO) display behavioral alterations such as hyperlocomotion and abnormal prepulse inhibition. However, it is possible that dopaminergic imbalances may have different effects during varied neurodevelopmental windows. In our previous study, we observed that elevated levels of dopamine during the perinatal developmental window increased exploratory behavior of juvenile (4-week-old) Swiss female mice and impaired hedonic behavior in males. In this study, we investigated whether these behavioral alterations persist through young adulthood. In order to do so, we administered daily doses of l-Dopa to mice pups beginning from postnatal day 1 (PD1) to PD5. At the age of 8 weeks, we submitted the young adult males and females to the open field test, elevated plus maze, forced swimming test, and sucrose preference test. We observed that augmentation of dopamine levels during the perinatal developmental window increased locomotor behavior in females, but not males. We also observed an increase in anxiety-behavior in females and anxiolytic-like behavior in males. In addition, we observed stress-coping behavior in males and an increase of hedonic behavior in females. Our results show that dopamine signaling is important for behavioral development and that transient imbalances of dopamine levels can cause permanent behavioral alterations - alterations which are different in males than in females. These data may help in better understanding the spectrum of symptoms associated with different neuropsychiatric disorders.

Seizure Susceptibility Corrupts Inferior Colliculus Acoustic Integration.

Evidence suggests that the pathophysiology associated with epileptic susceptibility may disturb the functional connectivity of neural circuits and compromise the brain functions, even when seizures are absent. Although memory impairment is a common comorbidity found in patients with epilepsy, it is still unclear whether more caudal structures may play a role in cognitive deficits, particularly in those cases where there is no evidence of hippocampal sclerosis. This work used a genetically selected rat strain for seizure susceptibility (Wistar audiogenic rat, WAR) and distinct behavioral (motor and memory-related tasks) and electrophysiological (inferior colliculus, IC) approaches to access acoustic primary integrative network properties. The IC neural assemblies' response was evaluated by auditory transient (focusing on bottom-up processing) and steady-state evoked response (ASSR, centering on feedforward and feedback forces over neural circuitry). The results show that WAR displayed no disturbance in motor performance or hippocampus-dependent memory tasks. Nonetheless, WAR animals exhibited significative impairment for auditory fear conditioning (AFC) along with no indicative of IC plastic changes between the pre-conditioning and test phases (ASSR coherence analysis). Furthermore, WAR's IC response to transient stimuli presented shorter latency and higher amplitude compared with Wistar; and the ASSR analysis showed similar results for WAR and Wistar animals under subthreshold dose of pentylenetetrazol (pro-convulsive drug) for seizure-induction. Our work demonstrated alterations at WAR IC neural network processing, which may explain the associated disturbance on AFC memory.