Neuroscience of Eating & Drinking PSYC 417

Brain and Behavior

The brain integrates internal and external information to guide decision and behavior. How is Central Nervous System organized to control behavior?

• signal transduction from action potential to muscle contraction to behavior

• In-depth discussion on the neural mechanisms of ingestive behaviors (anything you take - food, drink, drugs)

Sensory input

carried through sensory AFFERENT neurons

motor movement

Signal descended out to EFFERENT motor neurons

Foods: Sensation and Perception

• sensory inputs that detect and modulate the flavor (multi-sensory modality) of foods

What are consumers getting in the three-michelin-starred “The Fat Duck” restaurant

Flavor: Taste, Smell, Texture (touch), vision, sound (hear)

Some is hard-wired, some is not

Flavor preference influenced by cognitive process, based on experience. Through experience, associate sensory with flavor (Doritos are good if they make a crunch sound)

sensory modality hard-wired

smell

sensory modality not hard-wired

vision - associate

Food flavor

the flavor of foods is a multi-sensory perception

flavor perception involves

biological and cognitive process

biological process

inherent, hard wired, unconditioned, no previous exposure or learning needed

cognitive process

conditioned, learned, based on previous experience

Biological process (bottom-up)

ascending information that processes chemical senses in the CNS (the brain)

cognitive process (top-down)

descending influence (from the brain) or flavor perception and preference

sensation

detection, biological process

perception

adds cognition + your interpretation

Biological Bases of flavor

• when most people talk about “taste,” they are referring to flavor, which is composed by the combination of smell, taste, and oral somatosensory signals

• smell, taste, and trigeminal sensation together are referred to as chemical senses

• chemical senses are critical to our rewarding experience from foods

Smell (olfaction) is unique

perceived and evaluated in two qualitatively different ways - orthonasal olfaction and retronasal olfaction

orthonasal olfaction

breathe in through nasal cavity from external world

retronasal olfaction

volatile molecules released from food in the mouth

Food flavor sensation

without learning, the flavor of foods involves retronasal olfaction, taste, and oral somatosensory

without learning

retronasal

with learning

orthonasal

the keys to understand sensory guided behaviors

sensory detection, processing, and guided behaviors

sensory detection (sensation)

• receptor cells and receptors

• intracellular signal transduction

sensory processing

• sensory neurons ad neural coding

• ascending neural pathways to the cortex (perception)

• network with other brain regions

sensory guided behaviors

how does disruption of sensory processing affect behavior

lecture one review

• top down is associated with prior experience

• food flavor is a multi-sensory modality (all 5, not just 1)

• when learning is involved, all 5 senses contribute to the perception of food flavor, the color of food and sound of food affect flavor preference (top-down)

• trigeminal system contributes to the detection and perception of foods, volatile molecules can be detected via orthonasal and/or retronasal olfactory pathway

on average, the unique smell of a food item comes from the mixture of how many odorant molecules?

230

how does smell contribute to food preferences and feeding behaviors?

olfaction, taste, and oro (or oral)-somatosensory are primary components of flavor

what is the key function of smell?

important fro survival: designed to discriminate wheter the external stimulus is safe (familiar) or dangerous

what is unique about smell?

• detects and perceive airborne, volatile (evaporates) molecules/chemicals

• most mysterious! we can discriminate but cannot describe well

• permanent total loss of smell (anosmia) is rare

total loss of smell

anosmia

How do we measure smell or any sensory experience?

psychophysics

psychophysics

• measures subjective experience with well defined stimuli. It is a method to objectively assess sensory function

psychophysical tests measure sensory…

detection threshold, identification, discrimination

psychophysics tests include

stiffin sticks or olfaction and taste strips for taste (gustation)

Odor discrimination capacity

how do we use an experiment to estimate the number of different smells that our olfactory system is set up to discriminate

• a study using psychophysics rendered an estimation of > 1 trillion different smells of discrimination capacity

olfactory system programmed to have very high smell capacity (potential) - actual ability is far lower

Olfactory Receptor (OR) Cell

• nerve fibers of OR cells form the first pair of cranial nerves, which are nerves that emerge from the brain or the brainstem

• several cranial nerves are involved in eating and drinking

• cranial nerves are not entirely sensory nerves, some pairs/bundles sensory or motor or both!

Olfactory Processing

Olfactory Receptor Genes

• OR genes distributed throughout the genome

• clusters of various sizes and variable at sequence level

• OR genes not represented in chromosomes 8, 20, Y

Odorant receptors (OR)

• located at the olfactory epithelium, cilial membrane

• g protein coupled receptor (GPCR) - olfactory sensors all

• approx. 390 functional ORs identified in humans

• approx. 1500 functional ORs indentified in rodents, 100s of putative non-functional ORs

Does an odor smell the same to everyone?

Individual variations in OR genes (alleles) and OR neurons contribute to an individually unique sense of smell

• single nucleotide polymorphisms (SNP) in just one OR gene can have dramatic effects: specific hyperosmia, specific anosmia

Olfactory Receptors

• odorants bind to ORs

• one OR can recognize multiple odorants

• One odorant is detected by multiple ORs

• Different odorants are recognized by different combinations of ORs

• OR cells regenerate over a period of weeks throughout the lifespan so permanent anosmia is rare

Olfaction and Neurodegeneration

Neurogenesis in adults (olfactory epithelium, subgranular zone (hippocampal dentate gyrus), subventrical zone)

• olfaction decline is a symptom of multiple diseases: Alzheimer’s, Parkinson, schizophrenia

• smell detection test is being proposed for early diagnosis of Alzheimer’s disease

Olfactory Bulb

• both dogs and rodents have vomeronasal organ that detects pheromones, mostly non-volatile, which triggers sexual and social behaviors

• adult humans do not have a functional vomeronasal organ

• in proportion to the entire brain, humans have smaller olfactory bulbs than dogs and rodents

olfactory processing

• axons of olfactory receptor neuron (cranial nerve 1) projects to the main olfactory bulb

• In the olfactory bulb: glomeruli, mitral cells, tufted cells, local interneurons (granule cells and periglomerular cells

• each glomerulus contains inputs from a single type of odorant receptor (i.i., each neuron expresses a single OR gene)

glomerulus

clusters of synapes, NOT cell bodies

olfactory processing

zone to zone projection from olfactory epithelium to olfactory bulb

• each unique smell comes from a combination of neuronal activity in one or multiple zones of the olfactory epithelium and olfactory bulb

anatomical organization: to project to olfactory bulb, 4 zones (olfactory bulb is zoned too)

Odor Masking

• use odorants/volatiles to mask off-flavor commonly found in juice, meat, fish (alkylamines) or even human body odor

• spoiled fish, fennel, and clover trigger differential glomeruli responses in rats that are visualized via optical imaging

Odor masking

• glomeruli activated by spices are distant from those activated by spoiled odorants, but how does the spices mask the bad odor

• odor masking is mediated, in part, by lateral inhibitory connections in the odor masking maps of the olfactory bulbs

glomeruli activation are not actually close to each other - masking referring to smell neurons mitral cells activity being inhibited by another molecule. How if so far? Interneurons

Lateral Inhibition within the Olfactory Bulb

• mitral/tufted (M/T) cells receive input from olfactory receptor (sensory) neurons

• Periglomerular, EPL, granule cells are interneurons

• interneurons receive input from M/T cells, then produce feedback(lateral) inhibition to M/T cells

• Refine odor response/perception

Approx how many receptor genes

400 receptor genes → 400 different types of OR. Spread this out, 100 clusters in each area - divide into 4 areas, don’t mix zones

odorant masking….

does not prevent receptor binding

Olfactory Pathway

all projections from the olfactory bulb are ipsilateral

OR cell → olfactory bulb → piriform cortex, entorhinal cortex, amygdala → orbitofrontal cortex, hippocampus

olfactory system bypasses….

THALAMUS - thalamus involvement indirect in olfactory

unique to the olfactory system: with sensory processing, normally see the thalamus. Olfactory system bypass thalamus and goes directly to the cortex. Also bypasses the brainstem. Another unique thing → all projections ipsilateral. Contralateral projection (pass through other side) for most sensory perception. NOT with olfactory

Cortical Olfactory Representation

Olfactory Processing

• Inputs from different types of glomeruli in different zones of the olfactory bulb overlap extensively in the cortex

• Each cortical neuron receives signal derived from multiple types of glomerulus and zones in the olfactory bulb, so projections from olfactory bulb to the cortices do not follow a zone-to-zone projection pattern that appears in projections from the olfactory epithelium to the olfactory bulb

In the cortex…

no zone to zone projection

How does covid-19 impair smell

Covid-19 (CoV-2) induces acute loss of ciliation in the olfactory epithelium of Syrian hamster

Functional Tests (COVID)

• within 3 days post COVID infection, hamsters had increased latency to find hidden cereals and decreased 2% sucrose preference

after 14 days, cillian membrane is back. impacts preference to sucrose → lower preference

How does loss of smell affect appetite and body weight?

Can we use smell loss during a covid or covid-19 to assess the effects of olfaction on appetite and body weight

Olfaction Elimination

Temporary

• nostril ZnSO4 (zinc sulfate) treatment

• olfactory nerve transection

• genetic ablation to olfactory receptor neurons

  • mice with olfactory nerve transection cannot express preference for high fat diet

Permanent

• olfactory bulbectomy

  • bulbectomy altered mean patterns without changing total daily food intake

Olfaction and Eating

“smelling your food makes you fat” eye catching but not accurate and fair

Olfaction and Energy Balance

In mice with genetic ablation of olfaction neurons:

• resistant to diet-induced-obesity or lose weight without drastic reduction in food intake (OMP: olfactory marker protein)

olfaction and Energy Balance

Use CRISPR to enhance excitability of mitral/tufted projection neurons in mice

• food intake and locomotor activity are similar

• decreased body fat composition and body weight in male mice

Not often linear - looking for the extreme but there’s middle ground

Human olfactory disorders

congenital anosmia

infection or injury induced anosmia or hyposmia

parosmia (pregnancy)

phantosmia

• subjects with smell dysfunction may enjoy food less, have diminished appetite, and lose weight. However, increased food intake and weight gain have also been reported

congenital anosmia

born without a sense of smell

parosmia

distorted odor perceptions in the presence of an odor source

phantosmia

odor percepts without an odor present

Lecture 2 Summary

• tje results of how olfactory elimination affects appetite and body weight have been inconsistent across animal models and human studies

• The olfactory system may modulate pathways critical to the regulation of feeding and energy balance. Compared to the taste system, it does not appear to be essential for eating and drinking behaviors and the control of body weight