Molecular Neuroscience

Question 1

How many different genes are expressed in the brain?

Answer 1

30,000

Question 2

How many different types of proteins are there in the brain?

Answer 2

100,000

Question 3

There are how many neurons in the brain?

Answer 3

86 billion

Question 4

How many synapses are there in the brain?

Answer 4

10-100 trillion

Question 5

What timescale does brain response and signaling operate on?

Answer 5

A micro-millisecond timescale

Question 6

What is the major excitatory neurotransmitter?

Answer 6

Glutamate

Question 7

Which is the major inhibitory neurotransmitter?

Answer 7

GABA

Question 8

Which enzyme converts glutamate into GABA

Answer 8

Glutamic acid Decarboxylase (GAD)

Question 9

What are the three main structure elements of the Cytoskeleton

Answer 9

1. Microtubules
2. Actin filaments
3. Intermediate filaments

Question 10

What are microtubules made off?

Answer 10

A dimer protein of an alpha and beta subunits

Question 11

What is the role of actin filaments in the cytoskeleton?

Answer 11

Actin filaments, also known as microfilaments, are thin fibers that help in cell movement, shape, and division. They form the contractile ring during cytokinesis and contribute to muscle contraction in muscle cells. Actin is also involved in cell signaling and the formation of cell junctions.

Question 12

What is the molecular basis of multiple sclerosis (MS)?

Answer 12

Autoimmune attack on myelin sheaths, leading to impaired electrical signaling.

Question 13

How do mutations in ion channels contribute to neurological disorders?

Answer 13

Mutations can cause channelopathies, such as epilepsy (altered sodium channel function) or ataxia (calcium channel defects).

Question 14

What is the molecular target of SSRIs used to treat depression?

Answer 14

SSRIs inhibit the serotonin transporter (SERT), increasing serotonin levels in the synaptic cleft.

Question 15

What role do transcription factors play in neural development?

Answer 15

They regulate the expression of genes required for neuron differentiation and specialization.

Question 16

What are the two main types of receptors in the nervous system?

Answer 16

Ionotropic receptors (ligand-gated ion channels) and metabotropic receptors (G-protein-coupled receptors).

Question 17

First step of synaptic transmission

Answer 17

Action potential invades presynaptic terminal
- Transmitters are stored in vesicles

Question 18

Second step of synaptic transmission

Answer 18

Depolarization causes voltage-gated calcium channels to open

Question 19

Third step of synaptic transmission

Answer 19

Influx of calcium ions

Question 20

Fourth step of synaptic transmission

Answer 20

Calcium ions trigger vesicles to fuse with membrane

Question 21

Fifth step of synaptic transmission

Answer 21

Transmitter is released into the synaptic cleft via exocytosis

Question 22

Sixth step of synaptic transmission

Answer 22

Transmitter binds to postsynaptic receptors on the postsynaptic membrane

Question 23

Seventh step of synaptic transmission

Answer 23

Opening or closing of postsynaptic channels

Question 24

Eighth step of synaptic transmission

Answer 24

Post synaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell

Question 25

Ninth step of synaptic transmission

Answer 25

Removal of neurotransmitters by glial uptake or enzymatic degradation Retrieval of vesicular membrane from plasma membrane

Question 26

What is slow axonal transport?

Answer 26

Slow axonal transport is the process by which cytoskeletal components (e.g., microtubules, actin filaments) and soluble proteins are transported along axons at a rate of about 0.1-0.3 mm per day. This process primarily moves proteins to the distal axon and synapses.

Question 27

What is fast axonal transport and how does it work?

Answer 27

Fast axonal transport moves large organelles, vesicles, and proteins along microtubules at rates of 200-400 mm per day. It is driven by motor proteins, with kinesin moving cargo in the anterograde direction (towards the synapse) and dynein in the retrograde direction (towards the cell body).

Question 28

What are some examples of second messengers in neuronal signaling?

Answer 28

- cAMP: Activates PKA; involved in synaptic plasticity. - IP3 and DAG: Activate Ca2+ release and PKC. - Ca2+ ions: Trigger neurotransmitter release and gene expression.

Question 29

What is synaptic plasticity, and why is it important?

Answer 29

Synaptic plasticity refers to changes in the strength or efficiency of synaptic connections. - LTP (Long-Term Potentiation): Strengthens synaptic connections; linked to learning and memory. - LTD (Long-Term Depression): Weakens synaptic connections; linked to synaptic pruning.

Question 30

What molecular mechanisms generate an action potential?

Answer 30

- Resting Potential: Maintained by Na+/K+ pump and K+ leak channels. - Depolarization: Na+ channels open, allowing Na+ influx. - Repolarization: K+ channels open, allowing K+ efflux. - Refractory Period: Inactivation of Na+ channels prevents immediate reactivation.

Question 31

How are neurotransmitters synthesized?

Answer 31

- Glutamate: Synthesized from glutamine via glutaminase. - GABA: Synthesized from glutamate via glutamic acid decarboxylase (GAD). - Dopamine: Synthesized from tyrosine via tyrosine hydroxylase and DOPA decarboxylase.

Question 32

How does calcium-calmodulin-dependent signaling function in neurons?

Answer 32

- Ca2+ influx activates calmodulin (CaM). - CaM activates CaMKII (Calcium/Calmodulin-dependent kinase II), crucial for synaptic plasticity. - Downstream Effects: Phosphorylation of AMPA receptors, leading to increased synaptic strength during LTP.

Question 33

What is the role of mTOR in neuronal function?

Answer 33

- mTOR (Mechanistic Target of Rapamycin): Regulates protein synthesis in response to synaptic activity. - Involved in synaptic plasticity, dendritic spine growth, and long-term memory formation. - Dysregulation linked to autism spectrum disorders and neurodegenerative diseases.

Question 34

What molecular events underlie long-term potentiation (LTP)?

Answer 34

1. Early Phase (E-LTP): - NMDA receptor activation → Ca2+ influx → CaMKII activation. - Phosphorylation of AMPA receptors increases receptor density at the synapse. 2. Late Phase (L-LTP): - Requires protein synthesis mediated by CREB (cAMP response element-binding protein). - Structural changes in dendritic spines for long-term memory.

Question 35

What is the role of the endocannabinoid system in the CNS?

Answer 35

Key Components: - Endocannabinoids (e.g., anandamide, 2-AG): Retrograde messengers. - CB1 Receptor: Inhibits neurotransmitter release by reducing presynaptic Ca2+ influx. - Modulates synaptic plasticity, pain, mood, and appetite.

Question 36

How does synaptic pruning occur at the molecular level?

Answer 36

- Microglia engulf weak or unnecessary synapses via complement system activation (e.g., C1q, C3). - Neuronal activity regulates pruning, strengthening active synapses while eliminating inactive ones. - Dysregulation implicated in schizophrenia and autism.

Question 37

What causes excitotoxicity in neurons?

Answer 37

- Excess Glutamate Release leads to overactivation of NMDA and AMPA receptors. - Ca2+ Overload triggers: - Mitochondrial dysfunction → ROS production. -Activation of proteases and nucleases → Neuronal death. - Common in stroke and traumatic brain injury.

Question 38

How do astrocytes regulate neurotransmitter levels?

Answer 38

- Glutamate Uptake: Through EAAT1/2 transporters, preventing excitotoxicity. - Recycling via Glutamine-Glutamate Cycle: Converts glutamate to glutamine for neuronal reuse. - K+ Buffering: Regulates extracellular potassium to maintain neuronal excitability.