Untitled Quiz

Signaling in the CNS

Signaling in health involves classical neuronal signaling, neuronal communication, and chemical mediators like acetylcholine (ACh), noradrenaline (NA), glutamate, and GABA. Learning and memory are also part of this process.
Signaling in disease focuses on neurodegenerative diseases, and specific drug targets for Alzheimer's disease.

Neuronal Signaling via Neurotransmitters

Nerve terminal depolarization triggers Ca2+ channel opening, allowing Ca2+ to trigger neurotransmitter (NT) release. New vesicles are generated, and autoreceptor interaction occurs. NT removal (uptake or breakdown) is important.
Post-synaptic response involves interacting ion channels and G protein-coupled receptors (GPCRs).

Integration Signaling Output

Synaptic input convergence (one neuron influenced by many) is a key aspect.
Synaptic output divergence (one neuron influencing many) is another key aspect.
Brain activity has an inhibitory function approximately 70% of the time.

Synapses and Neuronal Integration

Two types of synapses:
- Excitatory synapses cause excitatory postsynaptic potentials (EPSPs) via depolarization and Na+ influx, often involving acetylcholine or glutamate.
- Inhibitory synapses cause inhibitory postsynaptic potentials (IPSPs) via hyperpolarization and increased K+ or Cl- influx, often involving GABA receptors.

Types of Neurotransmitters

Various neurotransmitters exist, each with different structures and functions. Examples given include adrenaline, noradrenaline, dopamine, serotonin, GABA, acetylcholine, glutamate, and endorphins. The study notes indicate the functions of these neurotransmitters in stress response, mood, learning memory, and other processes.

Chemical Mediators in CNS

Neurotransmitters:
- Fast-acting, primarily working via ion channels (e.g., acetylcholine, GABA, glutamate).
- Slow-acting, primarily working via G protein-coupled receptors (e.g., noradrenaline, acetylcholine, dopamine).
Neuromodulators:
- Released by neurons or other cells, often working via G protein-coupled receptors.
- Include neuropeptides, histamine, nitric oxide (NO), and arachidonic acid (AA).
- Produce slower and more general effects, including effects on gene transcription and synaptic plasticity.
Neurotrophic factors:
- Influence neuronal growth and morphology via tyrosine kinases.

Control Cellular Processes (Sympathetic vs. Parasympathetic)

The body has two autonomic systems that largely counterbalance each other to create homeostasis – the sympathetic and parasympathetic nervous systems. These systems are related to fight-or-flight and rest-and-digest responses, respectively.

Cholinergic Transmission

Acetylcholine (ACh) is transported across synapses; a breakdown enzyme, acetylcholinesterase, breaks down ACh. Choline is then transported back into the axon terminal to form more ACh.

Action Acetylcholine (ACh)

Cholinergic neurons are widespread in the brain, affecting memory and blood pressure. Indirect effects via NO are also possible.
Two main types of ACh receptors:
- Nicotinic receptors (ion channels) mediate fast actions.
- Muscarinic receptors (GPCRs) are involved in slow responses (e.g., lowering heart rate).

Membrane-Bound Receptors

Muscarinic receptors (GPCRs) and nicotinic receptors (ion channels) are discussed, including how acetylcholine binds to them.

Ion Channel Opening

Nerve impulses trigger the release of 100-500 vesicles, leading to a sodium influx (Na+) that depolarizes the cell.

Ligand-Gated Ion Channels

The unique composition of subunits forms the basis of various ligand-gated ion channels with distinct functions in the CNS. These are used in epilepsy, Alzheimer's, schizophrenia, and anxiety, among other conditions.

Role of nAChRs in CNS Disease

Nicotinic acetylcholine receptors (nAChRs) are crucial in diverse CNS conditions. Variations in their composition directly affect the conditions.

Cholinergic Transmission

Details of cholinergic transmission, including the role of acetylcholine, its synthesis, release, and degradation are described, emphasizing its role in the CNS.

Noradrenergic Signaling

Noradrenaline (NE) release triggers a response, and the mechanisms for its removal (reuptake, metabolism via monoamine oxidase) are described and related to other processes and negative feedback mechanisms.

Re-uptake Neurotransmitter (NA) Metabolism

75% of NA is restored via a specific Na transporter (NET), completing the neurotransmitter signaling cycle. The associated metabolism is also described.

Negative Feedback → Control NA Release

Autoreceptors (α2) play a crucial role in reducing noradrenaline release.

Neuronal Signaling via Amino Acids

Glutamate, glycine, and GABA are fast neurotransmitters involved in excitatory and inhibitory actions in the nervous system. Details on their synthesis and role in the nervous system is provided.

Glutamate Receptors (iGluRs)

Ionotropic glutamate receptors (iGluRs), including NMDA, AMPA, and kainate receptors, are detailed. They are ligand-gated ion channels, mostly responsible for fast EPSPs and are critically involved in various CNS functions.

Ligand-Gated NMDA Receptors

Allosteric modulators, like glycine, significantly influence NMDA receptor function, regulating calcium influx.

Metabotropic Glutamate Receptors (mGluRs)

Metabotropic glutamate receptors (mGluRs) affect neuronal excitability and synaptic function, primarily via G proteins. Eight different types are described.

iGluRs and mGluRs in Learning and Memory

iGluRs and mGluRs are crucial for long-term potentiation (LTP) and learning and memory. Details of LTP and synaptic plasticity are discussed.

Synapses and Neuronal Integration

Synaptic function, specifically the role of chemical synapses in information processing, storage, and decision-making within the CNS is provided, with additional emphasis on long-term potentiation and its importance.

Dendritic Spine Dysgenesis and Brain Disorders

Dendritic spine dysgenesis is described, suggesting a link to certain brain disorders including tuberous sclerosis, Fragile X syndrome, and others.

Long-Term Potentiation (LTP) - Memory

The role of LTP in memory encoding, storage, and retrieval is discussed with emphasis on scaffolding PDZ proteins in the post-synaptic density (PSD) and related molecular mechanisms.