MDD, Optogenetics, Dopamine in Ventral Tegmental Area (VTA)

What is major depressive disorder (MDD)

Mood disorder causes PERSISTENT feelign of sadness and ANHEDONIA

What is anhedonia

Loss of interest in activities that would give pleasure (eating, hobbies, sports, sex, etc)

Signs vs symptoms?

Signs → things a clinician measures

SYmptoms → Patient description of what they’re feeling

What are some sumptoms of MDD?

Sadness, irritability, outbursts, tearfulness.

what is a model system. pros and cons of using mice?

species of animal or cell culture or computer model whatever that has been developed and validated over many years into experimentally powerful approach used to answer specific questions.

Mice reproduce fast, good to use,

cons are can’t ask how they feel and could be expensive

WHere are the 3 places that dopamine comes from?

1. Acruate nucleus

2. Substantia nigra compacta (SNc)

3. Ventral Tegmental Area (VTA)

What are the 3 pathways that the dopamine starts and goes to?

1. Arcuate Nucleus → Pituitary Gland

2. Substantia Nigra Compacta (SNc) → Striatal Areas

3. Ventral Tegmental Area (VTA) → MANY different places

What are the 6 places that Dopamine from the Ventral Tegmental Area go to?

1. Nucleus accumbens (NAc)

2. Frontal cortex

3. Hippocampus

4. Cingulate gyrus

5. Striatum

6. Amygdala

What are 7 roles/functions of dopamine?

1. motivation

2. motor behavior

3. memory

4. attention

5. synthesis/release of prolactin

6. reinforcement

7. Addiction (pleasure)

what happens when there is a decrease in dopamine signaling?

Dec dopamine signaling → Anhedonia (dec intrest/pleasure seeking)

What is the nucleus accumbens a major component of?

Component of the ventral striatum

What does the nucleus acumbens do when it gets dopamine?

Mediates emotional and motivational processing

Modulates reward and pleasure processing

serving as key limbic-motor interface

What are inpts to the nucleus accumbens?

Prefrontal cortex (higher thinking)

Hippocampus (spatial memory)

Amygdala (fear, emotion)
VTA (Dopamine)

What are outputs of the nucleus accumbens

Places that motivate you to “get up and get pleasure”

• Ventral Pallidum

• Hypothalamus

• Midbrain

• Motor effector sites

what is optogenetics

technique that uses light to control specific neuron activity via light activated channels

What are channelrhodopsins. What type of channel are they

Light-sensitive channels that open in response to special wavelength of light (blue → Stimulatory, yellow → inhibitory)

• NON-SPECIFIC cation channel (mainly depolarizes via sodium and calcium influx)

How does blue light open channel rhodopsin?

Blue light transforms molecule into from trans to cis formation, opening channel

What is Halo-rhodopsin, what does it do?

Inhibitory channel that does chlroine influx hyperpolarizing membrane

How did yellow light affect the mice in experiments?

made them depressed basically and have hopelessness.

Yellow light → activated halo-rhodopsin → INHIBITED VTA (dopamine production place) → Decrease in struggling to break free from hanging and preferance b/n sweet and normal → INDUCES MDD

How did BLUE light affect the mice in experiments?

blue light → activated channel rhodopsin → Depolarization → activates VTA → INCREASE in trying ot break free and wanting to eat the sweets → PREVENTS/REVERSES MDD

^ works even in already depressed