Reversible inactivation of the lateral hypothalamus reversed high reward choices in cost-benefit decision-making in rats

Abstract

The Lateral hypothalamus (LH) is an important component of the networks underlying the control of feeding and other motivated behaviors. Cost-benefit decision-making is mediated largely by the prefrontal cortex (PFC) which strongly innervates the LH. Therefore, in the current study, we conducted a series of experiments to elucidate the role of the perifornical area of the lateral hypothalamus (PeF-LH) in effort and/or delay-based decision-making. We trained different groups of rats in a delay-based and/or an effort-based form of cost-benefit T-maze decision- making task in which they could either choose to pay the cost to obtain a high reward in one arm or could obtain a low reward in the other arm with no cost. During test days, the rats received local injections of either vehicle or lidocaine4% (0.5 μl/side), in the PeF-LH. In an effort-based decision task, PeF-LH inactivation led to decrease in high reward choice. Similarly, in a delay-based decision task animals' preference changed to a low but immediately available reward. This was not caused by a spatial memory or motor deficit. PeF-LH inactivation modified decision behavior. The results imply that PeF-LH is important for allowing the animal to pay a cost to acquire greater rewards.

The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation

“…Genetic deletion of the neuronal calcium sensor-1, which reduces accumbens DA transmission, made mice less willing to work for food, but left food preference, responding for conditioned reinforcement, and the ability to represent changes in reward value intact (Ng et al, 2016). Inactivation of the lateral hypothalamus produced a low-effort bias as marked by a reduction in barrier climbing in the T-maze (Karimi et al, 2017). Glycine acts as both an inhibitory neurotransmitter and a co-agonist at the N-methyl-D-aspartate receptor, and recent studies indicate that the glycine uptake inhibitor bitopertin can reverse the effort-related effects of haloperidol in rats tested on the FR5/chow-feeding and T-maze barrier choice tasks (Yohn et al, 2017a).…”

A Novel Weight Lifting Task for Investigating Effort and Persistence in Rats

“…The intensity of the effort can be increased by increasing the height of the barrier; maximum heights of 25 or 30 cm are most commonly reported. In rats, barrier paradigms have been used successfully in lesion/inactivation studies (Walton et al, 2002;Rudebeck et al, 2006;Floresco and Ghods-Sharifi, 2007;Holec et al, 2014;Karimi et al, 2017), pharmacological investigations (Schweimer and Hauber, 2006;Bardgett et al, 2009;Mott et al, 2009;Pardo et al, 2012;Yohn et al, 2015a,b;Correa et al, 2018), and electrophysiological recordings (Hillman and Bilkey, 2010;Cowen et al, 2012;Mashhoori et al, 2018) to assess the contribution of different brain areas and neurochemical systems to decisions that require physical effort. However, the protocol has limitations.…”

Differential Effects of the Lateral Hypothalamus Lesion as an Origin of Orexin and Blockade of Orexin-1 Receptor in the Orbitofrontal Cortex and Anterior Cingulate Cortex on Their Neuronal Activity

“…Our prior research showed that LH inactivation disrupts effort and delay-based decision-making task and this document clarified there is a relationship among ACC/OFC, as the two important sites for decision-making, and LH (Karimi et al, 2017). The alteration in the neural firing rate in ACC or OFC could also be due to the elimination of neurotransmitters in the LH.…”

“…Li, Hu, & Lecea, 2014). More recent works have revealed cognitive processes, such as associative learning and memory, control feeding behavior (Petrovich, 2018) and, decision-making (Karimi et al, 2017) need the LH function and it seems that it may serve as a motivation-cognition interface processor in the brain. Behavioral and electrophysiological studies have suggested the significance of the functional connections between the PFC and the LH (Arikuni, 1976;Kita & Oomura, 1981;Oomura & Takigawa, 1976).…”

“…Also, as mentioned above, LH is the main origin of orexin A and orexin B, containing neurons that are key regulators of different physiological functions, such as wakefulness ( Chen, de Lecea, Hu, & Gao, 2015 ; Li, Hu, & Lecea, 2014 ). Recent studies have revealed that cognitive processes, such as associative learning and memory, control feeding behavior ( Petrovich, 2018 ), and decision-making ( Karimi et al, 2017 ) require LH function. LH may serve as a motivation-cognition interface processor in the brain.…”