Sex and region-specific effects of high fat diet on PNNs in obesity susceptible rats.

Perineuronal nets (PNNs) are specialized extracellular matrix structures that primarily surround fast-spiking parvalbumin (PV)-containing interneurons within the PFC. They regulate PV neuron function and plasticity to maintain cortical excitatory/inhibitory balance. For example, reductions in PNN intensity are associated with reduced local inhibition and enhanced pyramidal neuron firing. We previously found that exposure to dietary high fat reduced PNN intensity within the PFC of male Sprague-Dawley (SD) rats. However, how high fat affects PNNs in the PFC of females or in obesity-vulnerable vs. -resistant models is unknown. Therefore, we gave male and female SD, selectively bred obesity-prone (OP), and obesity-resistant rats (OR) free access to standard lab chow or 60% high fat for 21 days. We then measured the number of PNN positive cells and PNN intensity (determined by Wisteria floribunda agglutinin [WFA] staining) as well as the number of PV positive neurons using immunohistochemistry. We found sex and region-specific effects of dietary high fat on PNN intensity, in the absence of robust changes in cell number. Effects were comparable in SD and OP but differed in OR rats. Specifically, high fat reduced PNN intensities in male SD and OP rats but increased PNN intensities in female SD and OP rats. In contrast, effects in ORs were opposite, with males showing increases in PNN intensity and females showing a reduction in intensity. Finally, these effects were also region specific, with diet-induced reductions in PNN intensity found in the prelimbic PFC (PL-PFC) and ventral medial orbital frontal cortex (vmOFC) of SD and OP males in the absence of changes in the infralimbic PFC (IL-PFC), and increases in PNN intensity in the IL-PFC of SD and OP females in the absence of changes in other regions. These results are discussed in light of roles PNNs may play in influencing PFC neuronal activity and the differential role of these sub-regions in food-seeking and motivation.

Consumption of a High-Fat Diet Alters Perineuronal Nets in the Prefrontal Cortex.

A key factor in the development of obesity is the overconsumption of fatty foods, which, in addition to facilitating weight gain, alters neuronal structures within brain reward circuitry. Our previous work demonstrates that sustained consumption of a high-fat diet (HFD) attenuates spine density in the prefrontal cortex (PFC). Whether HFD promotes structural adaptation among inhibitory cells of the PFC is presently unknown. One structure of interest is the perineuronal net (PNN), a specialized extracellular matrix surrounding, primarily, parvalbumin-containing GABAergic interneurons. PNNs contribute to synaptic stabilization, protect against oxidative stress, regulate the ionic microenvironment within cells, and modulate regional excitatory output. To examine diet-induced changes in PNNs, we maintained rats on one of three dietary conditions for 21 days: ad libitum chow, ad libitum 60% high fat (HF-AL), or limited-access calorically matched high fat (HF-CM), which produced no significant change in weight gain or adiposity with respect to chow controls. The PNN "number" and intensity were then quantified in the prelimbic (PL-PFC), infralimbic (IL-PFC), and ventral orbitofrontal cortex (OFC) using Wisteria floribunda agglutinin (WFA). Our results demonstrated that fat exposure, independent of weight gain, induced a robust decrease in the PNN intensity in the PL-PFC and OFC and a decrease in the PNN number in the OFC.

A method for evaluating cocaine-induced social preference in rats.

Drug addicts are extremely sensitive to cues that predict drug availability and exposure to these cues can facilitate drug relapse. Cues vary in their nature but can include drug-associated paraphernalia, environmental contexts, and discrete conditioned stimuli (e.g., advertisements). One cue that has recently been heavily investigated is that of social interaction. To date, it has been demonstrated that when cocaine is conditioned with social interaction, place preference for cocaine significantly increases, suggesting that the presence of social interaction during a drug-associated "high" enhances the magnitude of drug reward. When social interaction is provided in a mutually exclusive, non-drug environment though, it can serve as a preventative stimulus towards cocaine seeking. What remains unknown is whether contact with rats associated with drug experience facilitates preferential social interactions for those rats. The first step in answering this question is to determine if rats can behaviorally discriminate between drug-associated and non-drug-associated conspecifics, much like humans can differentiate their "drug-friends" from their non-drug-using friends. Using a custom social interaction chamber, in which rats were able to interact with two distinct conspecifics via holes in a boundary wall, we demonstrate that rats exhibit more interactive and investigative behavior towards a partner that was consistently present during the drug-state, than a partner that was present when the rat was "sober". It is our hope that this protocol will contribute to the development of models designed to study social cue-induced reinstatement, and related neural substrates, and will ultimately contribute to the treatment of substance use disorders.