Neuroscience of Motivation Exam II

What are the neurobiological substrates in which CALORIES/ENERGY motivate eating?

CALORIES AND TASTE lead to higher dopamine firing in:

The Substantia Nigra Pars Compacta (SNc) → The Dorsal Striatum

What are the neurobiological substrates in which TASTE/SWEETNESS motivate eating?

TASTE/SWEETNESS lead to higher dopamine firing in:

The Ventral Tegmental Area (VTA) → The Ventrial Striatum (Nucleus Accumbens)

What is MICRODIALYSIS? What is a con of it? Within studies looking at the DA firing in the dorsal or ventral striatum, where is the MICRODIALYSIS probe inserted?

MICRODIALYSIS is a small probe with a SEMI-PERMEABLE MEMBRANE, including an INLET PERFUSATE that mimics extracellular fluid, and an OUTLET DIALYSATE that is saturated, containing new molecules/neurotransmitters collected from the semi-permeable membrane sample

• PROCESS IS VERY SLOW - not the best for hunger

PROBE is inserted in the striatum, rather than the VTA or the SNc to measure the amounts of DA in the CEREBROSPINAL FLUID

In HEDONIC vs NUTRITIONAL VALUE paper, what were the initial 4 experiments to establish separately controlled dopamine levels?

1. OBSERVING DA RELEASE IN VS, WITH SUCRALOSE (NON CALORIC) ON TONGUE + GLUCOSE (CALORIC) OR SUCRALOSE IN STOMACH

DA above baseline in VS irrespective of which solution was intra-gastrically administered

2. OBSERVING DA RELEASE IN DS, WITH SUCRALOSE ON TONGUE + GLUCOSE OR SUCRALOSE IN STOMACH

DA in DS increased above baseline only for glucose (caloric) - DS projecting dopamine cells are selectively sensitive to sugar

3. OBSERVING DA RELEASE IN VS AND DS, ADULTERED SUGAR SOLUTION WITH DENATONIUM BENZOATE (BITTER) + GLUCOSE IN STOMACH

Sugar adulteration reduces dopamine in VS (dipping below baseline), dopamine rising above baseline in DS - taste quality may gate ventral dopamine efflux

4. OBSERVING DA RELEASE IN VS AND DS, SUCRALOSE ON TONGUE + NON-CALORIC SUGAR IN STOMACH

DA in DS did not increase from baseline, DA in VS rose above baseline, as expected with results from previous 3 studies

Where do dopamine neurons act in the STRIATUM?

When dopamine is released into the striatum from either VTA or SNc, it binds to STRIATAL NEURONS/SPINY PROJECTIONS that are predominantly GABAergic

• These GABAergic neurons have dopamine receptors - differentiated between INDIRECT (with D2 inhibitory neuron receptors) vs DIRECT (with D1 excitatory neurons receptors) GABAergic neurons

As dopamine releases, it binds to both types of receptors, but there are varying affects once it binds (D1 excitatory or D2 inhibitory)

Explain the D1-Cre rat

In genetically-modified D1-Cre rats:

• Neurons such as STRIATAL/SPINY NEURONS have D1 receptors

• CRE RECOMBINASE, is genetically engineered into the rat in order to read VIRAL DNA MATERIAL to unlock and activate D1-specific light-sensitive channels within the cell for OPTOGENETICS

What are findings related to hungry rats mice and unpalatable solutions/

HUNGRY MICE consumed significantly more of an unpalatable (bittered) solution when associated with caloric intra-gastric glucose, compared to non-caloric sweetener

• hungry mice endure unpalatable solutions when they are associated with energy, an effect mirrored by artificially increasing extracellular DA in DS or VS (energy and sweetness)

In HEDONIC vs NUTRITIONAL VALUE paper, what are the 4 experiments relating to D1 neurons and Cre-dependent caspase in D1-Cre mice?

In order to test whether STRIATAL dopamine mediated the organization of the basal ganglia pathways of ENERGY and TASTE through D1 excitatory receptors

1. LOSS-OF-FUNCTION ABLATION THROUGH CRE-DEPENDENT CASPASE IN VS (TASTE RESPONSES) AND DS (CALORIC RESPONSES), USING SUCRALOSE AND DENATONIUM BENZOATE

Mice with ablations in the VS were more sensitive to bitter solution (less licks) compared to DS casp or WT casp mice

• similar to findings of increasing concentrations of sweetener yo mask bitterness

2. LOSS-OF-FUNCTION ABLATION THROUGH CRE-DEPENDENT CASPASE IN VS and DS, USING FIXED BITTER SOLUTION AND INCREASING CONCENTRATION OF GLUCOSE IN STOMACH

DS CASP mice had an abolished sugar-induced consumption of palatable solutions - no compensation with calories for worsened taste effects

When glucose was low, VS CASP mice were far more affected by bitterness (less licking) compared to DS casp or WT casp mice

• When glucose was high, DS CASP mice failed to display changes in licking

• DS CASP mice did not lick upalatable solutions