Reward, Emotion, & Sleep

Reward

A natural process during which the brain associates diverse stimuli (substances, situations, events or activities) with a positive or desirable outcome

Subjective value

The way each individual evaluates the worth of an option or choice based on their own personal preference and context

Orbitofrontal Cortex (OFC)

A brain region that receives inputs from reward-related dopamine neurons and integrates sensory inputs to represent the reward value of food to help coordinate behavior

Reward System

The neural network consisting of multiple interacting neural circuits that receives and evaluates the rewarding properties of stimuli

Reward Prediction Error (RPE)

The difference between what was predicted and what actually happened when executing a behavior

Positive RPE

Occurs if what materialized is better than predicted, leading to reward learning and increased motivation

Negative RPE

Occurs if what materialized is worse than predicted, leading to decreased dopamine signaling and decreased motivation

Hedonic circuits

Neural circuits that actively apply pleasure onto sensations to generate a 'liking' reaction, without being driven by metabolic need

Appetitive phase

The phase of eating dominated by 'wanting' that involves initiating food procurement and foraging

Consummatory phase

The phase of eating dominated by 'liking' that involves engaging with food consumption

Satiety phase

The phase of eating that involves satiation and terminating food intake

Liking

The hedonic or pleasure component of reward that requires opioid and endocannabinoid signaling in the Nucleus Accumbens rather than dopamine

Wanting

The motivational component of reward that is generated by dopaminergic pathways

Aphagia

A state in which subjects lack the motivation to obtain rewards and will not engage in behaviors to obtain food or drink

Endogenous opioids

Neuropeptides that include enkephalins, dynorphins, and endorphins

Opioid receptors

G-protein coupled receptors with subtypes including mu, kappa, and delta

Endogenous endocannabinoids

Lipid molecules such as anandamide and 2-arachidonoylglycerol (2-AG)

Cannabinoid receptors

G-protein coupled receptors with subtypes CB1 and CB2, where CB1 is predominantly expressed in the central nervous system

Hedonic hotspots

Specific interconnected zones in the brain, such as within the Nucleus Accumbens, where mu opioid receptor activation causes enhanced hedonic responses and increased liking reactions

Fos plume

An experimental approach used to map functional connectivity between hotspots by injecting a drug and quantifying the expression of c-Fos in surrounding brain regions

c-Fos

A protein expressed when neurons are activated, providing a readout for increased neuronal activity

Major dopamine pathways

Brain pathways including the Mesolimbic/Mesocortical pathway and the Nigrostriatal pathwa

Emotion

A conscious brain function subjectively experienced as a strong feeling usually directed toward a specific object and typically accompanied by physiological and behavioural changes in the body

Diencephalon

The reptilian part of the brain whose central role in the expression of emotion is highlighted by transection experiments

Conditioned fear

The association between two stimuli (such as an auditory tone and a foot shock) that increases amygdala outputs

Long term potentiation (LTP)

A strengthening of glutamate synapses that supports conditioned fear learning, which can be inhibited by NMDA receptor antagonists

Hebbian mechanisms

Memory mechanisms that are important in the biological expression of emotion

Patient SM

A human patient with amygdala atrophy who exhibited a reduced fear response

Ventral Tegmentum

A brain region associated with reward

Caudate

A brain region associated with motivation

Glutamate receptors

Excitatory cation channels made of four subunits with a glutamate binding site on the outside

PSD-95

A molecule on the inside of the postsynaptic cell that binds to glutamate receptors

Glycine (GABA) receptors

Inhibitory anion channels made of five subunits with a glycine binding site on the outside

Gephyrin

A molecule on the inside of the postsynaptic cell that binds to glycine (GABA) receptors

Affective disorders

Conditions associated with dysfunctional emotional states, such as depression, mania, and anxiety

Depression

An affective disorder characterized by a low mood

Mania

An affective disorder characterized by an exaggerated elevated mood

Anxiety

An affective disorder characterized by the inappropriate activation of fear pathways and increased output from the amygdal

Sleep

An altered state of consciousness characterized by reduced movement and responsiveness, typical posture, homeostatic regulation, and daily rhythmicity

Sleep in higher animals

Characterized by specific brainwave patterns, loss of muscle tone, and sporadic eye movement

beta (b) activity

Brainwaves during the first hour of sleep with a frequency of 15-60 Hz and amplitude of ~30μV

theta (q) waves

Brainwaves during the first hour of sleep with frequencies of 4-8 Hz (50-100μV), 10-12 Hz (50-150μV), and 2-4 Hz (100-150μV)

delta (d) waves

Slow brainwaves during sleep with a frequency of 0.5-2 Hz and amplitude of 100-200μV

NREM Sleep

A sleep phase characterized by reduced physiological activity, a shift to parasympathetic activity, and maintained thermoregulation

Aging and Sleep

As humans age, they retain a similar amount of REM sleep but experience diminishing stage 3 and 4 deep sleep and increasing sleep fragmentation

Sleep Cycle

A cycle where REM periods occur every 90-120 minutes, the first REM period is the shortest, most REM sleep occurs late, and most deep sleep (stages 3, 4) occurs early

REM sleep

A sleep phase involving dreaming where brain activity, heart rate, and respiration resemble a wake state, but eye movement, muscle tone, thermoregulation, and genital responses diverge

VLPO / MPOA

Brain regions utilizing GABA that are "on" during NREM and REM sleep to help regulate the sleep/wake toggle switch

TMN

TuberoMammillary Nucleus, a brain region producing histamine (His) that is "on" during wakefulness and "off" during sleep

LH

Lateral Hypothalamus, a brain region producing orexin (ORXN) that is "on" during wakefulness and "off" during sleep

LC

Locus Coeruleus, a brain region producing norepinephrine (NE) that is "on" during wakefulness and "off" during sleep

Raphe

A brain region producing serotonin (5-HT) that is "on" during wakefulness and "off" during sleep

vPAG

ventral PeriAqueductal Gray, a brain region producing dopamine (DA) that is "on" during wakefulness and "off" during sleep

LDT / PPT

LateroDorsal / PedunculoPontine Tegmental Nucleus regions producing acetylcholine (ACh) that are "on" during wakefulness and REM sleep, but "off" during NREM sleep

Sleep Deprivation Symptoms

Physical signs include a debilitated appearance, skin lesions, swelling paws, loss of motor control, respiratory symptoms, and stomach ulcers

Cognitive impact of Sleep disruption

Mental effects include inattention, slower computational speed, impaired verbal fluency, reduced creativity, impaired abstract problem solving, learning issues, and lower IQ scores

Primary Insomnia

A sleep disorder affecting 1-10% of the population with sudden onset, characterized by initial phase anxiety or middle phase maintenance issues, frequently affecting women and the elderly in a vicious cycle

Narcolepsy

A sleep disorder caused by an orexin signaling defect, resulting in daytime sleepiness, sleep attacks, cataplexy triggered by emotions, sleep paralysis, and excessive dreaming

Obstructive Sleep Apnea

A breathing-related sleep disorder caused by a blocked airway, leading to decreased blood oxygenation and waking, which increases the risk of cardiovascular disease, diabetes, and depression

Circadian Rhythm Sleep Disorders

Conditions including Non-24h sleep wake syndrome, irregular sleep wake syndrome, delayed sleep phase syndrome, and advanced sleep phase syndrome

Process C

The circadian rhythmic control of sleep

Process S

The homeostatic control of sleep, related to sleep debt

Chronomedicine

The study of how disruptions to circadian rhythms (via jet lag, shift work, or artificial light) lower health and well-being, increasing risks for cancer, diabetes, obesity, stroke, heart disease, and depression

Evidence for Circadian Clock

Demonstrated through the control of overt rhythms, entrainment, free-running rhythms, and temperature compensation

Molecular Clockwork

The delayed negative feedback of gene expression responsible for circadian timing

Drosophila Molecular Clock

CLK and CYC activate transcription at the E-box, while PER and TIM repress it

Mammalian Molecular Clock

CLOCK and BMAL1 activate transcription at the E-box, while mCRY and PER act as repressors

SCF Complex

A system utilizing E3 ubiquitin ligases to mediate the degradation of clock proteins like PER

Light-dependent TIM degradation

A process where light causes the degradation of the TIM protein involving CRY, modifying the circadian phase

Phase Delay

Caused by light exposure in the early night or late dusk, shifting the circadian rhythm backward

Phase Advance

Caused by light exposure in the late night or early dawn, shifting the circadian rhythm forward

s-LNv, LNd, and DN1

Circadian clock neurons in Drosophila that synchronize using neuropeptides such as sNPF and PDF

PPM3 DA neurons

Dopamine neurons that connect s-LNv and LNd to the Ellipsoid Body (EB) Ring 2 Neurons, required for sleep/wake rhythms

Pars Intercerebralis (PI)

A neurosecretory structure targeted by DN1 neurons to release Diuretic Hormone 44 (DH44)

HUG cells

Cells located in the Subesophageal Zone (SEZ) that receive DH44, feed back negatively on PDF s-LNvs, and regulate sleep/wake rhythms via the ventral nerve cord

REM

Rapid Eye Movement

EOG

ElectroOculoGram

EMG

ElectroMyoGram

5-HT

5-Hydroxytryptamine (Serotonin)

GABA

Gamma-Aminobutyric Acid