Neuroscience Fundamentals

Nervous System - Continuing

• First Exam: Scheduled for 8:45 AM on February 10, 2024. An optional online review session is available on February 9th at 8:00 PM.

Presynaptic Events

• IPSPs and EPSPs passively travel through the cell body and dendrites without voltage-sensitive channels.

• The axon hillock is the summation point for these signals.

• Voltage-sensitive channels are concentrated at the axon hillock.

• An action potential (AP) is generated if the signal reaches threshold at the axon hillock.

• Nerve Impulse Propagation: The nerve impulse travels down the axon to the axon terminal.

Presynaptic Events - Calcium Channels

• Calcium channels are present in the cell membrane near axon terminals.

• These channels are voltage-dependent, opening in response to action potentials.

• The action potential opens calcium channels, allowing calcium ions to flow into the axon terminal.

• Synaptic Vesicles: When calcium channels open, calcium ions cause synaptic vesicles to fuse with the presynaptic membrane.

• Neurotransmitter Release: Fused vesicles release neurotransmitters into the synaptic cleft, the space between neurons. Neurotransmitters are chemical messengers.

In the Synaptic Cleft

• The synaptic cleft isn't empty but contains guiding molecules.
• The presynaptic portion is the axon terminal, and the postsynaptic is the cell body/dendrite.

Postsynaptic Events

• Neurotransmitters bind to receptor sites on the postsynaptic cell, similar to a key fitting into a lock.
• This binding initiates a neural message.

Ionotropic Receptors

• Neurotransmitter binding opens an ion channel, allowing ions to flow into the postsynaptic cell.
• Ions flow through the channel when the neurotransmitter attaches. Neurotransmitters are larger than individual ions.

Ionic Movements During Postsynaptic Potentials

• Influx of Na+ causes depolarization (EPSP).
• Efflux of K+ causes hyperpolarization (IPSP).
• Influx of Cl- causes hyperpolarization (IPSP)
• Influx of Ca2+ activates enzymes, leading to various effects.

Metabotropic Receptors

• Neurotransmitter binding to a receptor triggers a chain of chemical events.
• This ultimately indirectly affects an ion channel or causes another change within the cell.

Activation of Receptors

• The movement of ions like sodium and potassium between, and inside the cell.

Termination of Postsynaptic Potentials

• Reuptake: Rapid removal of neurotransmitters from the synaptic cleft by the terminal button.
• Enzymatic Deactivation: Enzymes break down neurotransmitters. Acetylcholinesterase deactivates acetylcholine.

Neurotransmitters and Drugs - Some Examples

• Psychoactive Drugs: Alter mood, thought, or behavior, used to manage neuropsychological illness, and exert an effect on the brain. To be psychoactive, a drug must influence the nervous system.

The Blood-Brain Barrier

• Small, non-ionized, fat-soluble molecules like oxygen and CO2 can pass through the blood-brain barrier easily.
• Larger molecules, such as glucose and amino acids, require active transport systems to cross the barrier.
• The blood-brain barrier prevents free passage of substances from the blood into the brain.

Why Have a Barrier?

• Precise ion concentrations are crucial for neuronal electrical activity.
• Protects the brain from toxic and infectious substances.

A Clinical Example - Treating Parkinson's Disease

• Dopamine is vital but cannot cross the blood-brain barrier in its natural form.
• L-DOPA, a similar chemical compound, can pass through and is used to treat Parkinson's disease.

Effects of Psychoactive Drugs

• Agonist: Increases the effectiveness of neurotransmitters at the synapse.
• Antagonist: Decreases the effectiveness of neurotransmitters at the synapse.

Alcohol as an Example

• Alcohol affects neurotransmitters glutamate and GABA.
• Alcohol prevents glutamate from acting (antagonist), while making GABA more inhibitory (agonist).
• Greatest effect in the brain’s frontal regions impacting impulse control, decision making, and memory.

GABA - Major Inhibitory NT of CNS

• GABA (gamma-aminobutyric acid) produces an influx of chloride ions (Cl−) into the postsynaptic cell.

• This influx hyperpolarizes the membrane and makes it less likely to produce an action potential.

• Alcohol and GABA: Alcohol acts like GABA, increasing chloride conductance.

Rohypnol (Roofies) + Alcohol = Very Bad

• Rohypnol is a benzodiazepine used as a sedative-hypnotic.
• The combination of Rohypnol and alcohol can be extremely dangerous.

The "Reward" Circuit

• The "reward" circuit is associated with dopamine release and feelings of pleasure.
• Natural rewards like food, sex, and thirst stimulate the reward circuit.
• Drugs and gambling also can activate this circuit.

A "Natural High"

• Opiate receptors serve to reduce pain naturally.
• GABA normally inhibits dopamine release to some degree.

Heroin

• Heroin binds to opiate receptors, decreasing GABA action and increasing dopamine release.
• Heroin is a highly effective, potentially harmful opiate-like drug. Other examples of opiate-like drugs are oxycodone, hydrocodone, methadone, and Fentanyl.

Cocaine

• Cocaine works on dopamine receptors, stopping dopamine reuptake into the presynaptic axon terminals.

The Nervous System on a Large Scale

The Structure of the Nervous System

• CNS (Central Nervous System): Brain and spinal cord.
• PNS (Peripheral Nervous System): Structure outside the brain and spinal cord. The CNS communicates to other parts of the body through nerves.

Nerves

• A nerve is a bundle of axons surrounded by a sheath.
• Outside the brain and spinal cord, these bundles of axons are nerves. Inside the brain and spinal cord they are called tracts.

Anatomical Directions

• Rostral-Caudal: Anterior-Posterior. Rostral (towards the front) and Caudal (towards the tail).
• Ventral-Dorsal: Ventral (belly-side) and Dorsal (backside).
• Medial-Lateral: Medial (towards the middle) and Lateral (towards the sides).

Examples of Anatomically Defined Structures

• dorsolateral prefrontal cortex
• ventromedial hypothalamus

2d --> 3d

• Different ways to look at the brain structure (frontal, horizontal, saggital, transverse).

Surface Features - Meninges

• The meninges are tough layers covering the brain.
• Three layers: Dura mater, Arachnoid mater, Pia mater.
• Subarachnoid space (filled with cerebrospinal fluid).

Ventricles and Cerebrospinal Fluid (CSF)

• Ventricles are interconnected hollow chambers in the brain that produce and contain CSF.

Brain is Fragile

• The brain is soft, jellylike and needs protection.
• Cerebrospinal Fluid (CSF) is a shock absorber around the brain. It reduces weight and pressure.

Concussion and Chronic Traumatic Encephalopathy (CTE)

• CTE is a progressive brain condition linked to repeated head injuries and blows.
• Head injuries worsen over time and lead to dementia.

Test your knowledge of neuroscience, covering topics such as meninges, cerebrospinal fluid (CSF), brain anatomy, and synaptic transmission. Questions cover CTE, receptors, neurotransmitters, and neural processes.