Hippocampal Leptin Signaling Reduces Food Intake and Modulates Food-Related Memory Processing

Abstract

The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 mg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 mg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.

Leptin Signaling in the Medial Nucleus Tractus Solitarius Reduces Food Seeking and Willingness to Work for Food

“…2a. The procedures for appetitive CPP were as we have previously described (Kanoski et al, 2011). All CPP training and testing procedures were conducted in a dimly lit room.…”

“…Historically, attention has been directed toward leptin's action in the hypothalamus, particularly the arcuate hypothalamic nucleus (ARC). More recent findings reveal that leptin's powerful control over energy balance is anatomically distributed (Grill, 2010;Grill and Kaplan, 1990;Grill and Kaplan, 2002a) as it involves contributions from midbrain and forebrain regions such as the ventral tegmental area (Fulton et al, 2006;Hommel et al, 2006) and the hippocampus (Kanoski et al, 2011) that are associated with the control of motivational, learned, and rewarding aspects of food intake, as well as in extra-ARC hypothalamic nuclei (Leinninger et al, 2009;Zhang et al, 2011) and hindbrain nuclei (Grill et al, 2002b;Huo et al, 2007;Schwartz and Moran, 2002;Skibicka and Grill, 2009) whose neural processing is typically associated with the control of need-based food intake (ie, feeding driven by energy deficit). Within the hindbrain, the LepRb is most densely expressed in the medial nucleus tractus solitarius (mNTS) of the dorsal vagal complex (Caron et al, 2010;Elias et al, 2000;Huo et al, 2006;Li et al, 1999;Patterson et al, 2011), which is the first CNS site to receive vagal afferentmediated gastrointestinal (GI) signals and is a critical nucleus for satiation signal processing and meal size control Schwartz, 2010).…”

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

“…Glial proteins were upregulated in the hippocampus, but not in the cerebellum, suggesting that the effects could be related to metabolic control, as the hippocampus is involved in food-seeking and food-memory behaviors (54,77), with leptin targeting this brain area and modulating these effects (77). Moreover, HFD modifies glutamate uptake and metabolism in the hippocampus (78).…”

Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

“…The hypothalamus is the main brain region integrating peripheral metabolic information controlling the homeostatic regulation of appetite and food intake 70,71 . The hippocampus is a brain structure involved in learning and memory function and has recently been linked with food intake control 72 . In addition, the 5-HT2C receptor is strongly expressed in the hippocampus and on pro-opiomelanocortin (POMC) expressing neurons in the arcuate nucleus of the hypothalamus as well as in other hypothalamic regions 48,49,73,74 .…”