NBL 355 Module 9

The process by which neurons communicate with each other through electrical and chemical signaling at specialized junctions called synapses. Involves the release, diffusion, and binding of neurotransmitters to receptors.

Synaptic Transmission

Jan Swammerdam's frog neuromuscular preparation to Luigi Galvani's discovery of the action potential in the late 1700s led to the ____________________.

Discovery of Synaptic Transmission

The hypothesis about the function of the nervous system in the early 1700s, centered around the idea of ________ advocated by Galen and originating from the Ancient Greeks.

Animal Spirits

_________________’s idea in the early 1700s was that nerve signals have an electrical nature, thus describing the concept of electric bodies and the role of electricity in nerve signal transmission.

Isaac Newton

Italian doctor and professor of anatomy who helped discover the action potential using frog neuromuscular junction. He published a commentary on electricity's effects on muscular motion in 1791 and is thus considered a pioneer of electrical signaling in the nervous system.

Luigi Galvani

The development of ________ in the 1600s and 1700s by scientists like Van Leeuwenhoek, Odierna, and Hook, leading to the identification and description of neurons and nervous tissue by anatomists like Valentin, Ehrenberg, Purkinje, and Remak.

Microscopy

___________ and __________, who used a stain to visualize cells in the nervous system, with ________ proposing the reticular theory and ___________ proposing the neuron doctrine and the concept of synapses.

Golgi; Cajal; Golgi; Cajal

The concept proposed by Santiago Ramon y Cajal that cells in the brain are separate entities communicating at specific junctions called synapses, in contrast to Golgi's reticular theory suggesting physical connections between cells.

Neuron Doctrine

The region between neurons or between a neuron and its target cell where transmission occurs, involving both electrical and chemical signaling, identified as the primary site of communication in the nervous system.

Synapse

A type of synaptic transmission where there is direct flow of current between the presynaptic axon and the postsynaptic neuron through gap junctions, allowing for rapid communication without the use of neurotransmitters. Allows direct flow of ions between pre- and post-synaptic regions through connexons, enabling fast communication but lacks adaptability.

Electrical Synapse

A type of synaptic transmission where neurotransmitters are released from the presynaptic axon into the synaptic cleft, bind to specific receptors on the postsynaptic membrane, and induce responses in the target cell, which can be excitatory, inhibitory, or modulatory.

Chemical Synapse

Large channel or pore-like complexes formed between the plasma membrane of the presynaptic axon and the postsynaptic cell in electrical synapses, allowing for the direct movement of small molecules, including ions, between the cells.

Gap Junctions

Channels composed of connexin proteins located on the presynaptic and postsynaptic membranes in electrical synapses, allowing for the flow of ions and small molecules directly across the gap junction channels.

Connexons

A type of neurotransmission where neurotransmitters are released into the synaptic cleft but can diffuse outside into the extracellular fluid, affecting multiple neurons or dendritic spines in the surrounding area, leading to coordinated responses in a volume around the release site.

Volume Transmission

Astrocytes help compartmentalize synaptic transmission by producing extracellular proteins that form barriers to neurotransmitter diffusion, ensuring specificity in wiring transmission.

Astrocyte function at the synapse

Inhibitory synapses, excitatory synapses, and modulatory synapses are functional types named based on the response in the postsynaptic cell, with the presynaptic axon always communicating and using action potentials.

Types of synapses in the central nervous system

Spine synapses on dendritic spines are predominantly excitatory using glutamate, while shaft synapses on dendritic shafts can be excitatory, inhibitory, or modulatory, with GABA as the main inhibitory neurotransmitter.

Morphological types of CNS synapses

A type of synapse where a presynaptic axon forms functional synapses with multiple target dendritic spines along its path, contributing to synaptic transmission and information integration within neurons. The axon continues past the synapse to form connections with multiple downstream targets.

En passant synapse

The synaptic cleft is closer than depicted, with cell adhesion molecules spanning the pre and postsynaptic membranes, forming homotypic or heterotypic interactions that stabilize synaptic connections and enable communication beyond synaptic transmission.

Synaptic cleft and cell adhesion molecules

Role of cell adhesion molecules in autism

Mutations in neurexins and neuroligins, involved in forming synaptic connections, were the first genetic mutations identified in individuals with autism, highlighting the importance of these proteins in synaptic function and communication.

Involves the presynaptic neuron, postsynaptic neuron, and astrocyte, emphasizing the role of astrocytes in determining synaptic transmission as point-to-point or volume transmission.

Tripartite synapse

Long-term potentiation leads to changes in dendritic spines, receptor numbers, and synaptic responses, contributing to _________ crucial for learning and memory in both developmental and adult brains.

Synaptic plasticity

The first identified neurotransmitter, discovered by Dr. Otto Loewi, involved in mediating synaptic transmission.

Acetylcholine

A parasympathetic nerve originating in the brain stem, involved in regulating heart rate and contraction force.

Vagus Nerve

Proteins on the postsynaptic membrane that NTs bind to, leading to changes in membrane potential or the production of second messengers.

Neurotransmitter Receptors

Neurotransmitters with low molecular weight, synthesized in presynaptic terminus, stored in synaptic vesicles, and can produce rapid or slow effects. Consists of small proteins, synthesized in the cell body, transported to presynaptic terminus in dense core granules, and produce neuromodulatory effects. Categorized into amines, amino acids, and purines based on their molecular structure.

Small Molecule Neurotransmitters

Larger neurotransmitters that are released further away from active zones, diffusing into extracellular fluid without specific uptake or degradative mechanisms.

Neuropeptide Neurotransmitters

Hydrophobic molecules like endocannabinoids and small molecule gases (e.g., nitric oxide) that are not stored in vesicles, can diffuse across membranes, and are usually neuromodulatory.

Unconventional Neurotransmitters

Structures that store neurotransmitters before their release, with _________ (smaller, clear) storing small molecule neurotransmitters and _______ (larger, dense core) storing neuropeptides.

Synaptic vesicles; Secretory vesicles

Small molecule transmitters with amino groups, including acetylcholine and biogenic amines like dopamine and serotonin.

Amines

Larger precursors of neurotransmitters cleaved by proteases, synthesized in the cell soma, and released from secretory vesicles.

Neuropeptides

Transported by vesicular neurotransmitter transporters using a proton gradient. Generated from synaptic endosomes, containing neurotransmitters and released at the presynaptic terminus for synaptic transmission.

Synaptic vesicles

Concept of neurotransmitter release in discrete units within synaptic vesicles, with 3,000-9,000 molecules per vesicle. When an action potential reaches the presynaptic terminal, it triggers the release of synaptic vesicles, leading to the release of neurotransmitter into the synaptic cleft. Each synaptic vesicle releases its neurotransmitter content in a quantal fashion, ensuring that the amount of neurotransmitter released at each vesicle fusion event is consistent This phenomenon allows for precise and reliable synaptic transmission between neurons.

Quantal release

Electrical signal triggering neurotransmitter release by activating VGCCs in the presynaptic region. A rapid change in the membrane potential of a neuron, involving depolarization and repolarization, essential for transmitting signals. The electrical signal that requires activation of voltage-gated Na+ and K+ channels, conducted along the axon causing depolarization of the presynaptic membrane.

Action potential

Synaptic connection where the axon terminates at the postsynaptic target.

Terminal synapse

Channels activated by depolarization, leading to calcium influx and triggering neurotransmitter release in the presynaptic neuron. Transmembrane proteins in the presynaptic neuron that open in response to depolarization, allowing calcium influx and neurotransmitter release. Contains an Alpha subunit with 12 transmembrane spanning domains, S4 regions, and auxiliary subunits for localization. Also detect presynaptic action potentials and convert them into a release of neurotransmitters through calcium-dependent exocytosis. Channels composed of 24 transmembrane domains, activated by depolarization to about -45 to -40 mV, allowing Ca2+ influx triggering exocytosis of synaptic vesicles.

VGCCs

A divalent cation that acts as a messenger molecule and plays a crucial role in synaptic transmission by triggering neurotransmitter release.

Calcium Ion

N-type and P/Q-type channels in presynaptic region for neurotransmitter release, L and T-type channels in muscle cells and dendrites with different functions.

Calcium influx and neurotransmitter release

Proton ATPase pumps protons, vesicular neurotransmitter transporter fills vesicles, synaptotagmin senses calcium, V-SNARE and synaptophysin aid in fusion.

Synaptic vesicle proteins

Resting pool, recycling pool, and readily releasable pool connected metabolically for efficient neurotransmitter release.

Synaptic vesicle pools

_______ binds calcium, induces conformational change, and communicates with the ________ complex for vesicle fusion and exocytosis.

Synaptotagmin; SNARE

Docking of vesicle, priming through SNARE complex formation, calcium influx leading to vesicle fusion, exocytosis, and neurotransmitter release into synaptic cleft.

Neurotransmitter release process

A rapid fusion process where synaptic vesicles fuse with the presynaptic membrane quickly, allowing for rapid endocytosis and recycling of neurotransmitters.

Ultrafast Fusion

The process by which cells absorb molecules by engulfing them with their cell membrane, crucial for recycling synaptic vesicles and maintaining presynaptic membrane integrity. Process where the membrane is retrieved after exocytosis, allowing for recycling of synaptic vesicle proteins and lipids, and refilling with NT.

Endocytosis

Regions within the presynaptic neuron where voltage-gated calcium channels are localized, leading to high calcium concentrations and neurotransmitter release.

Calcium Microdomains

A key feature where VGCCs do not inactivate, allowing for faithful transduction of action potential frequency into presynaptic calcium levels and neurotransmitter release.

Prolonged opening of Calcium Channels

Mechanisms such as degradation and transporters that remove neurotransmitters from the synaptic cleft, crucial for terminating synaptic transmission.

Neurotransmitter Removal

The process of retrieving and recycling synaptic vesicle proteins after neurotransmitter release, involving endocytosis and refilling with neurotransmitters for reuse.

Synaptic Vesicle Recycling

Proposed by Camillo Golgi, suggests that cells in the nervous system form a continuous network allowing unimpeded electrical signal flow.

Reticular Theory

Involves conversion of electrical signals to chemical information via neurotransmitter release, offering adaptability and varied responses.

Chemical Synapse

Point-to-point neurotransmission localized at synapses, either through electrical responses (EPSPs, IPSPs) or volume transmission.

Wiring Transmission

Three functional types of synapses based on their effects; anatomical types include axo-dendritic, axo-somatic, and axo-axonic synapses.

Excitatory, Inhibitory, Modulatory Synapses

Molecules crucial for synaptic formation, maturation, and plasticity, enhancing trans-cellular communication at synapses.

Synaptic Adhesion Proteins

Process in which synapses are strengthened, weakened, or removed in an activity-dependent manner, crucial for learning and memory.

Synaptic Refinement

Small molecule and neuropeptide _________, including acetylcholine, monoamines, amino acids, and purines, crucial for synaptic communication.

Neurotransmitters

Divalent cation crucial for neurotransmitter release, regulated by pumps and exchangers to maintain low intracellular levels and prevent cell death.

Ca2+ Regulation

Caused by presynaptic Ca2+ increase, mediated by synaptotagmin binding to Ca2+ and SNARE complex formation, leading to NT release into the synaptic cleft.

Synaptic Vesicle Fusion

Mechanisms to keep intracellular Ca2+ levels low after influx through VG Ca2+ channels, involving pumping out, binding to proteins, and sequestration into organelles.

Presynaptic Ca2+ Regulation

Encoding of information in AP frequency, pattern, and number, decoded by VG Ca2+ channels to determine presynaptic Ca2+ signal and NT release.

Neural Coding

Small molecule NTs released by low frequency APs near active zones, while neuropeptide NTs require high frequency APs for release further away.

NT Release Regulation

Mechanisms including diffusion, degradation by proteases, and uptake into neurons and astrocytes by transporters to ensure short-lived and specific neuronal responses.

NT Removal

The discovery of synapses and synapses transmission involved and required the discovery or development of ____.

All of these answers

Tissue dyes/stains

Muscle contraction in response to electrical stimulation

The microscope and cell

Electricity

All of these answers

An electrical synapse requires _______.

Neurotransmitter release

Postsynaptic neurotransmitter receptors

Presynaptic voltage gated Na+, K+ and Ca2+ channels

Synaptic vesicles

Direct contact between the presynaptic and postsynaptic membranes

Direct contact between the presynaptic and postsynaptic membranes

A chemical synapse requires ____.

Release of neurotransmitter into the synaptic cleft or extracellular fluid

Direct contact between the presynaptic and postsynaptic membranes

Flow of current through GAP junction channels

Formation of a postsynaptic action potential

Synthesis of neurotransmitter in the synaptic cleft

Release of neurotransmitter into the synaptic cleft or extracellular fluid

Synapses can occur between a presynaptic neuron and ___.

A cardiac muscle cell

Another neuron

All of these answers

A neurosecretory (gland) cell

A smooth or skeletal muscle cell

All of these answers

Compared to electrical synapses, chemical synapses _____.

All of these answers

Are more abundant

Are more adaptable

Require more steps

Are slower

All of these answers

In ______ transmission, neurotransmitter can diffuse out of the synapse and activate nearby spines or neurons.

Diffuse

Point to point

Volume

Endocrine

Wiring

Volume

Which of the following BEST DESCRIBES typical synapses in the CNS?

The postsynaptic region of the synapse forms on dendrites but not other regions of the neuron

The presynaptic region of the synapse can be an axon or a dendrite

A synapse can include an oligodendrocyte which forms part of the tripartite synapse

Synapses can contain cell adhesion molecules and extracellular matrix proteins

In en passant synapses the axon ends on its target

Synapses can contain cell adhesion molecules and extracellular matrix proteins

Since axons can branch and form en passant synapses, this ensures that a neuron can communicate ____.

In volume and wiring transmission

With skeletal muscle and organs in the periphery

In both the CNS and PNS

Through chemical and electrical synaptic transmission

With multiple target neurons and at multiple synapses

With multiple target neurons and at multiple synapses

Acetylcholine was the first neurotransmitter identified through its release by the ______ and effects in the ______.

Autonomic ganglion, smooth muscle

Sympathetic nerve, aorta

Vagus nerve, heart

Brainstem, parasympathetic nervous system

Motor neurons, skeletal muscle

Vagus nerve, heart

The three categories of small molecule neurotransmitters are the _____, _________, ________.

Amines, Amino Acids, and Purines

Small molecule neurotransmitters are synthesized in the ____ and packaged into ____.

Presynaptic region, synaptic vesicles

Presynaptic region, secretory vesicles

Cell body/soma, secretory vesicles

Cell body/soma, synaptic vesicles

All of these answers

Presynaptic region, synaptic vesicles

Vesicles are filled with small molecule neurotransmitters (NTs) by _____.

The H+ (proton) ATPase pump

NT channels

Translocation in the RER

Endocytosis of NTs

Vesicular NT transporters

Vesicular NT transporters

Which of the following BEST DESCRIBES synaptic vesicles (SVs)?

SVs contain the v SNARE and t SNARE proteins

SVs contain the Ca2+ sensor called syntaxin

SVs contain both small molecule and neuropeptide neurotransmitters

SVs contain ion channels and ion transporters

SVs contain the proton/H+ ATPase and neurotransmitter transporters

SVs contain the proton/H+ ATPase and neurotransmitter transporters

Neuropeptides are synthesized in the ____ and packaged into ____.

Cell body/soma, synaptic vesicles

Presynaptic region, secretory vesicles

All of these answers

Presynaptic region, synaptic vesicles

Cell body/soma, secretory vesicles

Cell body/soma, secretory vesicles

Conventional NTs include both small molecule NTs and neuropeptide NTs.

True

False

True

Small molecule neurotransmitters and neuropeptides differ in their___.

All of these answers

Localization and release site in the presynaptic region

Molecular mass

Site of synthesis in the neuron

Requirements for release from the presynaptic neuron

All of these answers

In general, it has been shown that each neuron synthesizes and releases _____, though there are some exceptions to this.

One type of amine, one type of amino acid AND one type of neuropeptide NT

One small molecule NT AND one neuropeptide NT

One small molecule NT OR one neuropeptide NT

All types of NTs packaged into different vesicles

Many types of NTs that are co-packaged into synaptic vesicles

One small molecule NT AND one neuropeptide NT

Which of the following BEST DESCRIBES Ca2+ in neurons?

Ca2+ is involved in conduction of the action potential at the presynaptic region

Intracellular Ca2+ levels are controlled primarily by secondary active transporters on the plasma membrane

Low intracellular levels of Ca2+ can lead to apoptosis, a type of cell death

The Ca2+ concentration ratio (outside/inside) is ~ 10 at rest

Ca2+ is neither synthesized nor degraded so its concentration is controlled by its localization

Ca2+ is neither synthesized nor degraded so its concentration is controlled by its localization

Which of the following BEST DESCRIBES VGCCs? VGCCs _____.

All of these answers

Are required to increase the intracellular Ca2+ levels that stimulate NT release

Contain four S4 voltage sensor transmembrane domains

Are localized to the active zone

Are activated by the depolarization produced by the action potential

All of these answers

Which of the following BEST DESCRIBES the release of small molecule NT? It involves ______.

Diffusion of NT through GAP junction channels

Activation of VGCCs located on synaptic vesicles

Plasma membrane NT transporters which are located at the active zone

Formation of the SNARE complex between v-SNARES and t-SNARES

Endocytosis of synaptic vesicles at the active zone

Formation of the SNARE complex between v-SNARES and t-SNARES

What determines how much neurotransmitter is released by a presynaptic neuron?

All of these answers

The pattern of APs in the AP train

The frequency of APs in the AP train

How many VGCCs are opened and for how long

The number of action potentials (length of the AP train)

All of these answers

After fusion of a synaptic vesicle with the presynaptic plasma membrane, the synaptic vesicle membrane is retrieved by the process of ______.

Synopsis

Synaptocytosis

Phagocytosis

Exocytosis

Endocytosis

Endocytosis

Which of the following IS NOT a mechanism that may be involved in removing NTs or decreasing NT levels at the synaptic cleft?

Endocytosis

Uptake by plasma membrane NT transporters

Diffusion

Degradation

Endocytosis

Endosomal trafficking in the presynaptic region is DIRECTLY required for____.

Retrieval of exocytosed synaptic vesicle membrane and generation of new synaptic vesicles

Degradation of the NT at the cleft

All of these answers

Removal of NT from the cleft

Exocytosis and release NT at the cleft

Retrieval of exocytosed synaptic vesicle membrane and generation of new synaptic vesicles

In the early to mid-1800s, scientists including Jan Purkinje used _____ to further the understanding of the nervous system.

Photography

All of these answers

Electrophysiology

Microscopy

Biochemistry

Microscopy

In the the late 19th and early 20th century, the major argument between those who favored the neuron doctrine (Cajal) or reticular theory (Golgi) is whether communication involves______.

Chemical or electrical synapses

Chemical or electrical signaling

Neurotransmitters or neuropeptides

Continuous physical connections or gaps between neuronal processes

Action potentials and graded potentials

Continuous physical connections or gaps between neuronal processes

The debate between the soups and sparks was about whether ______.

Reactions in the primordial soup were stimulated by sparks

Axonal conduction involve chemical or electrical changes

Synaptic potentials involve the movement of ions or electrons

Neurons evolved once or twice during evolution

Synaptic transmission involves chemical or electrical signals

Synaptic transmission involves chemical or electrical signals

Who was correct about the debate above?

Both the soups and the sparks

The soups

The sparks

Neither the soups nor the sparks

Both the soups and the sparks

In the majority of neurons, the presynaptic region is typically an axon. Which types of neurons communicate by synaptic transmission but don't have an axon?

Some neurons in ganglia in the PNS

Some motor neurons

All of these answers

Some neurons in nuclei in the CNS

Some sensory receptor cells

Some sensory receptor cells

The secretory pathway can impact synaptic transmission because ____are generated in the secretory pathway.

Neuropeptides

Plasma membrane proteins and lipids

Dense core vesicles and secretory granules

Synaptic vesicle precursors

All of these answers

All of these answers

Synaptic plasticity, which involves the formation. strengthening, weakening and pruning of synapses, can occur _____.

In several neuronal circuits of the CNS

In the adult brain

During development

As a mechanism in memory

All of these answers

All of these answers

It has been proposed that the molecular mechanism(s) that decodes the neural code is/are _____.

All of these answers

The activation of VGCCs

The conduction of the action potential

The formation of synaptic vesicles

The inactivation of VGNa+Cs

The activation of VGCCs

A neuron is often described by the __________.

All of these answers

Neurons that communicate with it

Neurons it communicates with

Small molecule and neuropeptide NTs it releases

Types of synaptic inputs it receives

Small molecule and neuropeptide NTs it releases

At an electrical synapse, there is ________.

Opening of gap junction channels by neurotransmitter binding

Neurotransmitter diffusion through GAP junction channels

Direct movement of current through GAP junction channels

All of these answers

Exocytosis of synaptic vesicles containing GAP junction channels

Direct movement of current through GAP junction channels

At a chemical synapse, the presynaptic action potential ________.

Usually leads to release of neurotransmitter into the synaptic cleft or extracellular fluid

Usually produces an action potential in the postsynaptic cell

Is usually produced by a Na+ current which diffuses directly into the postsynaptic neuron producing an EPSP

All of these answers

Usually activates the opening of GAP junction channels which increase Ca2+ levels and stimulate the SNARE complex

Usually leads to release of neurotransmitter into the synaptic cleft or extracellular fluid

Which of the following is NOT TRUE about synapses in the CNS? They can ________.

Contain cell adhesion molecules and extracellular matrix proteins

Occur on dendrites, dendritic spines, the cell body/soma or axon

Include an astrocyte which forms the tripartite synapse

Be terminal synapses or en passant synapses

Involve an oligodendrocyte which myelinates the synapse

Involve an oligodendrocyte which myelinates the synapse

Which of the following is NOT TRUE about chemical synapses? Chemical synapses __________.

Are more abundant than electrical synapses

Are more adaptable than electrical synapses since they involve neurotransmitters and receptors

Involve more biochemical steps than electrical synapses do

Produce slower synaptic transmission than electrical synapses do

Involve point-to-point transmission but electrical synapses do not

Involve point-to-point transmission but electrical synapses do not

You discovered a new synapse which by electron microscopy contains a 30 nm gap, but two regions where the presynaptic and postsynaptic membranes are so closely apposed that no gap is visible. It contains numerous 40 nm vesicles on the presynaptic region and a postsynaptic density. You suspect this is ________.

An electrical only synapse

A neuromodulatory synapse

A chemical only synapse

A mixed electrical and chemical synapse

A dendro-dendritic synapse

A mixed electrical and chemical synapse

In the early to mid-1800s, scientists including Jan Purkinje used _____ to further the understanding of the nervous system.

Photography

All of these answers

Biochemistry

Electrophysiology

Microscopy

Microscopy