Sinapsis y funcionamiento de las neuronas

Summary

El doctor Marco explica las bases de las neurociencias, centrándose en la fisiología de las neuronas y las sinapsis. Describe la estructura de las neuronas, su función especializada y cómo se comunican entre sí. Detalla los tipos de sinapsis, electricales y químicas, y sus implicaciones en la conductancia de impulsos neurales. Además, menciona enfermedades como la miastenia grave y el síndrome de Lambert-Eaton, y cómo el toxina botulínica afecta la liberación de neurotransmisores.

Takeaways

• 🧠 La neurociencia estudia la生理学 de las neuronas y las sinapsis, que son las bases del sistema nervioso central.
• 👨‍⚕️ El doctor Marco explica que las sinapsis pueden estar entre neuronas y también entre neuronas y otras células, como las sinapsis inmunológicas.
• 📚 La Teoría Reticular, que una vez predominaba, fue desacreditada en el siglo XIX, gracias a avances científicos que mostraron que el cerebro está compuesto de células especiales, las neuronas.
• 🏆 El científico Santiago Ramón y Cajal, utilizando el técnica de tintura de doble plata, descubrió que las neuronas eran las células responsables de las funciones cerebrales.
• 🌐 Las neuronas son células altamente especializadas que reciben y transmiten información de manera rápida y eficiente.
• 📍 Las neuronas tienen una estructura específica que incluye el soma, los dendritos, el axón y las telodendritas, cada uno con una función crucial en la transmisión de señales.
• 🔋 Las células de Schwann aisladas por mielina en el axón, permiten que la información se transmita de manera rápida y saltatoria.
• 🚚 Los sistemas de transporte especializados en las neuronas, como la proteína kinesina y la dineina, son esenciales para el transporte de proteínas y neurotransmisores.
• 🔄 El proceso de Wallerian degeneration describe cómo la porción distal de una neurona se degenera después de una lesión, mientras que la porción proximal puede regenerarse.
• 🔬 Hay cuatro tipos principales de neuronas según su forma y función: monopolares, bipolares, multipolares y pseudo-unipolares.
• 🔄 Las sinapsis son los lugares donde una neurona se comunica con otra, y existen dos tipos principales: sinapsis eléctricas y químicas, con diferentes formas de transmisión y velocidades.

Q & A

¿Qué es un neurona y qué papel desempeña en el sistema nervioso central?

Una neurona es una célula que compone el cerebro y el sistema nervioso. Tiene la capacidad de recibir, integrar y transmitir información de un lugar a otro de forma polarizada, esencial para la función del sistema nervioso central.

¿Cuál es la teoría Reticular y cómo cambió la comprensión del cerebro con el tiempo?

La teoría Reticular era una idea antigua que consideraba que el cerebro estaba formado por una red de conexiones continuas. Esta teoría prevaleció hasta el siglo XIX, cuando avances científicos la desacreditaron, demostrando que el cerebro está compuesto de neuronas individuales.

¿Quién fue Santiago Ramón y Cajal y qué contribuciones realizó a la neurobiología?

Santiago Ramón y Cajal fue un científico español que, usando el método de tintura doble de Golgi, descubrió que el cerebro está compuesto de células individuales llamadas neuronas, las cuales son fundamentales para todas las funciones cerebrales.

¿Cuáles son las partes principales de una neurona y cuál es su función?

Las partes principales de una neurona incluyen el soma, que contiene la mayoría de los organelos; los dendritos, que son ramificaciones delgadas para recibir señales; el axón, que transmite la señal a otras neuronas; y los telodendritos, que son las ramificaciones finales del axón.

¿Qué es la mielina y cómo ayuda en la transmisión de señales eléctricas en las neuronas?

La mielina es una sustancia grasa que recubre el axón de algunas neuronas. Aísla el axón, permitiendo que la información eléctrica se transmita de manera más rápida y eficiente a través de un proceso llamado conducción saltatoria.

¿Qué son las sinapsis y cómo funcionan en la comunicación entre neuronas?

Las sinapsis son los puntos de conexión entre neuronas donde ocurre la transmisión de señales. Existen sinapsis eléctricas y químicas; las primeras transmiten señales de manera directa a través de la membrana celular, mientras que las segundas utilizan neurotransmisores para transmitir la señal al neurona siguiente.

¿Cómo se produce la conducción saltatoria en las neuronas y qué importancia tiene?

La conducción saltatoria es un método de transmisión de señales eléctricas en neuronas mielinizadas, donde la señal 'salta' de un nodo de Ranvier a otro, permitiendo una transmisión rápida y eficiente a lo largo del axón.

¿Qué son los neurotransmisores y qué papel juegan en las sinapsis químicas?

Los neurotransmisores son sustancias químicas que se liberan de un neurona y se unen a receptores en la neurona siguiente, provocando una respuesta en esta última. Son esenciales para la comunicación entre neuronas en las sinapsis químicas.

¿Qué es la toxina botulínica y cómo afecta la función de las sinapsis?

La toxina botulínica es una sustancia que se une a las proteínas SNARE, evitando que los neurotransmisores se unan y se liberen a la sinapsis. Esto puede llevar a la parálisis temporal de los músculos afectados, y se utiliza en tratamientos como el Botox para reducir el movimiento excesivo en ciertos músculos.

¿Cuáles son las enfermedades myasthenia gravis y síndrome de Lambert-Eaton, y cómo se relacionan con las sinapsis?

La myasthenia gravis es una enfermedad autoinmune que causa la generación de anticuerpos contra los receptores de acetylcholina, lo que impide la contracción muscular. El síndrome de Lambert-Eaton es otra enfermedad autoinmune que bloquea los canales de calcio en las neuronas, evitando la liberación de neurotransmisores y provocando parálisis.

Outlines

00:00

🧠 Introducción a las Neurociencias

El doctor Marco inicia la clase presentando el tema de las neurociencias, enfocándose en la explicación de la fisiología de las neuronas y las sinapsis. Destaca la importancia de entender cómo estas células se conectan para dar lugar a los sistemas del sistema nervioso central. Aborda brevemente la teoría de la Teoría Reticular, que fue desacreditada en el siglo XIX gracias a avances científicos, especialmente el trabajo de Santiago Ramón y Cajal que reveló la existencia de las células como las neuronas, que son fundamentales para todas las funciones cerebrales.

05:03

🌐 Estructura y Funciones de las Neuronas

Se describe la estructura general de una neurona, incluyendo el soma, los dendritos, el axón, y las telodendritas. Se explica que las neuronas son células altamente especializadas con la función específica de recibir y transmitir información rápidamente de un lugar a otro. Además, se menciona la importancia de los glóbulos de mielina y las células de Schwann en la transmisión de la información a través del sistema nervioso, y cómo esto se ve afectado en casos de lesiones neurales.

10:03

🔄 Transporte y Comunicación en las Neuronas

El doctor Marco detalla el sistema de transporte especializado en las neuronas, donde las proteínas kinesina y dineina son responsables del transporte de proteínas y otros componentes desde el soma hacia las extremidades y viceversa. Se discute cómo las neuronas producen y transportan neurotransmisores a lo largo del axón para su liberación en la sinapsis, y cómo se produce la degeneración de Wallerian cuando se corta un nervio.

15:07

🔗 Sinapsis y sus Tipos

Se define la sinapsis como el lugar donde una neurona se comunica con otra, distinguiendo entre sinapsis eléctricas y químicas. Se explica cómo funcionan las sinapsis eléctricas a través de la conexión directa de los citoplasmas de dos neuronas y cómo esto se ve limitado por la distancia y la dispersión de los iones. Por otro lado, se describe la sinapsis química, que implica la liberación de neurotransmisores y su acción en los receptores post-sináptico, lo que introduce una demora en la transmisión neuronal pero permite una mayor modulación y control.

20:07

💊 Botulismo y Otras Patologías Relacionadas con las Sinapsis

Se discuten las enfermedades y toxinas que afectan la función de las sinapsis, como el toxina botulínica que impide la liberación de neurotransmisores bloqueando las proteínas SNARE. Se menciona cómo esto puede llevar a la parálisis y se exploran sus aplicaciones médicas, como en el tratamiento de la espasticidad y fines estéticos. También se mencionan enfermedades autoinmunes como la miastenia grave y el síndrome de Lambert-Eaton, que afectan la comunicación entre las neuronas y los músculos.

25:08

📚 Recursos de Aprendizaje y Conclusión de la Clase

El doctor Marco recomienda recursos adicionales para un estudio más profundo de los temas tratados en la clase, como artículos de Wikipedia, capítulos de libros específicos y recursos de neuroquímica básica. Finaliza la clase invitando a los estudiantes a dejar comentarios y preguntas, y anima a suscriptores a compartir el contenido para difundir el conocimiento.

Keywords

💡Neuronas

Las neuronas son células especializadas que componen el sistema nervioso. En el vídeo, se explica que las neuronas son fundamentales para entender la función cerebral, ya que son las unidades básicas que generan la consciencia, los recuerdos y las emociones. El doctor Marco describe cómo las neuronas se comunican a través de los dendritos y el axón, y cómo su activación puede transmitir información de un punto a otro en el cuerpo.

💡Sinapsis

La sinapsis es el punto de conexión entre dos neuronas donde ocurre la transmisión de la información. En el guion, se menciona que existen dos tipos principales de sinapsis: eléctricas y químicas. Las sinapsis químicas son fundamentales para el video, ya que implican la liberación de neurotransmisores y la activación de receptores en la neurona postsináptica, lo que permite la comunicación entre neuronas.

💡Reticular Theory

La Teoría Reticular es mencionada en el vídeo como una teoría pasada sobre la estructura del cerebro, donde se creía que existía una red continua de conexiones en todo el cerebro. Este concepto fue desacreditado en el siglo XIX, y su mención en el vídeo sirve para contrastar con el entendimiento actual de la organización neuronal y sináptica.

💡Golgi, Camillo

Camillo Golgi es recordado en el vídeo por su contribución al desarrollo del método de tintura de plata, que permitió observar por primera vez las células nerviosas. Su trabajo fue fundamental para la descripción de las neuronas como unidades individuales, lo que desencadenó un cambio en la comprensión de la biología neuronal.

💡Santiago Ramón y Cajal

Santiago Ramón y Cajal es reconocido en el vídeo como el padre de la neurobiología moderna. Su trabajo con el método de doble tintura de plata reveló la estructura de las neuronas y su papel en las funciones cerebrales, lo que estableció las bases para el estudio de las neuronas y las sinapsis.

💡Dendritas

Los dendritos son prolongaciones finas de la neurona que reciben señales de otras neuronas. En el vídeo, se describe cómo los dendritos se integran a la soma para procesar la información neuronal, y son esenciales para la función sináptica, ya que es a través de ellos que llegan los neurotransmisores desde otras neuronas.

💡Axón

El axón es la prolongación más gruesa de la neurona que transporta la señal neuronal lejos de la soma hacia otras células. En el vídeo, se explica que el axón está recubierto por mielina, lo que permite una conducción más rápida de la señal, y termina en telodendritas, donde se libera el neurotransmisor.

💡Mielina

La mielina es una sustancia grasa que recubre el axón de algunas neuronas y facilita la conducción de la señal eléctrica a través de un mecanismo llamado conducción saltatoria. En el vídeo, se menciona que la mielina es crucial para la velocidad y eficiencia de la transmisión neuronal en neuronas largas.

💡Neurotransmisores

Los neurotransmisores son las sustancias químicas que se liberan de los axones y atraviesan el espacio sináptico para activar la neurona postsináptica. En el vídeo, se discute cómo la liberación de neurotransmisores es controlada por la presencia de calcio y las interacciones de las proteínas SNARE.

💡SNARE proteins

Las proteínas SNARE son esenciales para la fusión de las vesículas que contienen neurotransmisores con la membrana de la neurona, permitiendo la liberación de los neurotransmisores en la sinapsis. En el vídeo, se describe cómo las proteínas SNARE y el calcio trabajan juntos para desencadenar la liberación de neurotransmisores en respuesta a la activación neuronal.

Highlights

Explicación de la fisiología de las neuronas y las sinapsis, y cómo se conectan para generar los sistemas del sistema nervioso central.

Menciona la posibilidad de preguntas en los comentarios y cómo responderá a ellas.

Historia de la teoría reticular y su rechazo en el siglo XIX.

Descubrimiento de la célula neuronal por Santiago Ramón y Cajal usando el método de tintura doble de plata.

Importancia de las neuronas en la generación de la conciencia, memorias, ilusiones y emociones.

Descripción de la estructura general de una neurona, incluyendo el soma, dendritas, axón y telodendritas.

Función especializada de las neuronas en la transmisión rápida y eficiente de información.

Mecanismo de integración de información en la neurona y decisión de activación o no.

Importancia del sistema de conducción salatoria y las células de Schwann en la transmisión de impulsos eléctricos.

Función del cono axonal en la transmisión de información eléctrica.

Descripción del sistema de transporte especializado en las neuronas mediante kinesina y dineina.

Explicación del proceso de degeneración de Wallerian y la regeneración de la neurona proximal.

Función de las vesiculas y la necesidad de calcio para la liberación de neurotransmisores.

Tipos de neuronas según su forma y función: monopolares, bipolares, multipolares y pseudo-unipolares.

Definición de una sinapsis y diferencia entre sinapsis eléctricas y químicas.

Características y limitaciones de las sinapsis eléctricas en la comunicación neuronal.

Mecanismo de liberación de neurotransmisores en las sinapsis químicas y su regulación por calcio.

Importancia de las proteínas SNARE en la fusión de las vesiculas con la membrana y liberación de neurotransmisores.

Aplicaciones del toxina botulínica en la medicina para el tratamiento de parálisis y para fines estéticos.

Descripción de enfermedades como la miastenia grave y el síndrome de Lambert-Eaton y su efecto en la función de las sinapsis.

Recomendaciones de recursos para obtener más información sobre neuronas y sinapsis.

Transcripts

Good evening, how are you? I'm doctor Marco

Today, we'll carry on with the basic sciences,

but now with the neurosciences,

we will basically explain the physiology of neurons

and the physiology of synapses, how they connect to each other

to generate all the systems we've been watching

in this of the central nervous system.

You know, if you have any questions leave them in the comments

and we answer them.

Let's find out what are neurons

and what are synapses.

Obviously, by studying the brain,

we found that neurons and synapses

are embedded in it,

although as we will see later,

synapses may also be present

between neurons and other cells

or only the ones who are independent from the central nervous system,

like the famous immunological synapses.

For a long time people thought of a theory

called Reticular Theory,

that the brain consisted

of a large network of many connections all over the place,

continuous between them,

that the information travelled through the whole brain

and that each of the parts of the brain

interpreted this new information in a different way,

giving it a final meaning.

This theory prevailed for a long time,

until the 19th century,

when some scientists generated sufficient progress

for this theory to be discredited.

First, there was the great scientist Golgi,

he designed a stain, called Silver Staining

in which he put silver in the cells

and watched how some of them would paint themselves

It was with this famous staining

that the father of today's neurobiology,

the scientist Santiago Ramón y Cajal,

developed a more advanced staining method,

called Double Silver Staining,

that, when applied to the brain for the first time,

he found these images.

These images revolutionized the scientific field

and specifically the biology field,

finding for the first time that these things,

which he would later describe as cells,

were the ones that generated all the functions in the brain.

The brain was made of these cells.

This is how he discovered and demonstrated

that all the secrets kept in the brain,

from our conscience, our memories,

our illusions, our emotions,

all were concentrated or were hidden

in the mystery that were these small cells called neurons,

generating, thus, the dogma of neurons,

which is the most used in today's neurosciences.

What are these specific neurons?

We already know that neurons are cells

of which our brain is composed of

and how the cells of the rest of the body

will have specific organelles

that allow you to develop certain activities.

We already saw this in a previous class,

we have a great amount of organelles.

Neurons will have exactly the same,

are going to have the core,

the rough and the smooth endoplasmic reticulum, the Golgi apparatus,

the mitochondria, etc,

but the neurons are not traditional cells,

they are highly specialized cells with a specific function.

If we had to mention

what are the most important functions

of most neurons,

they had to be these four, in general.

They quickly receive and transmit the information.

It is from one place to another, they start at one point

and transmit it to the other side in a polarized way,

it goes from point A to point B,

normally it does not go from point B to point A.

Sometimes this place is far away,

for example, in human beings the sciatic nerve

that transmits up to the leg,

can measure up to one meter,

which has to carry this message

and the neurons have to, in some way, integrate this information.

In this class, and in the subsequent classes,

we'll see how this is done.

If we study the general structure of these neurons,

we see that they have more or less this way.

Of course, has a lot of variability

depending on the function of the body part, etc,

but a prototype neuron has this shape.

Basically, it has the place where the core

and most of the organelles are,

which is called soma, this part here.

From the soma, there will usually come out one or several dendrites,

which are very thin ramifications that do not have organelles

or have very few organelles,

beyond the cytoplasm

and the microtubules that give it its structure.

From this soma,

there is going to be another thicker projection,

that will mostly be covered by fat,

a fat called myelin.

This little road, this whole duct

is going to be called an axon.

This axon is going to be prolonged until it reaches some very thin

ramifications called terminal axons

or that can also be called teledendrites.

Now, what connects the soma and the axon

is going to be called an axon cone

and it's going to be very important

in the transmission of electrical information.

We will see it ahead in other videos.

Basically, we are going to see

what happens a little bit further,

but it is that the stimulus reaches this neuron,

to the soma or even to the dendrites,

that's the most common.

A neuron sends its message to this

through its dendrites, that is the most common,

or it can also be done through the soma.

This is integrating the information from these,

not only from the one I just painted,

but, for example, there may be another neuron here

that sends you other message and another one over here.

This neuron is going to integrate.

Let's suppose all the blue ones inhibit this neuron,

the red one stimulates,

this neuron is going to be averaged, so to speak,

it decides whether to activate it or not.

When activated in the axon cone,

it begins the nerve transmission

until the teledendrites or the terminal axon

sends its message to a subsequent neuron.

Now, this one sends it to the next neuron,

so that the information passed from point A,

or from neuron A to neuron B

through the dendrite, the soma and the axon

to the C-neuron.

This, especially, in long neurons,

that are said to measure more than a meter or up to a meter,

it is very important to have a very efficient transmission system

and to make it a very fast system too.

Let's see the system in another class,

but basically what we have is that,

attached to this neuron in its axon,

we are going to have some cells called Schwann cells,

that are present in this axon isolating it.

They will isolate it, so that the electrical information

can travel much faster

in something called saltatory conduction

in these spaces that have no myelin

and, therefore, don't have any Schwann cells

called Ranvier nodes.

This is the general form of a neuron

and it is, in part, its operation.

Here it is again.

Now, this has important implications,

we are saying that inside the soma of the neuron

we have the most of the organelles,

and the core of the rough endoplasmic reticulum, etc.

That means that most of proteins

are produced in the soma, and not here.

However, if the communication with other neurons is here,

this part, where this neuron is,

must secrete the neurotransmitters.

This is a big problem because

if we have all the proteins inside the soma,

we need you them to travel through long distances

to the synaptic space,

to the synaptic cleft and the teledendrites.

How do you do it then?

What is the mechanism that this neuron has

to send everything it needs to the terminal axon

and to, this way, communicate efficiently?

We will have

a specialized transport system in the neurons,

which will mainly happen in the axons,

but the dendrites can also have it

and it will consist of two rails

or two very large transport systems.

One will be the kinesin protein

that will take everything from the soma to the periphery,

and in the opposite direction, we are going to have the dynein.

This dynein is going to send it from the periphery to the soma.

For example,

if we have a neuron that has to produce noradrenaline,

it has to send the enzymes

or it has to send something else,

so that, at this point, noradrenaline is produced.

It produces the enzymes here because here you have all your genes

and you have all your rough endoplasmic reticulum

for protein production,

Stick it on the little train what is the kinesin

and the kinesin takes it away and brings it here,

until it accumulates in this part, and noradrenaline is synthesized

so that later the vesicles, which are also produced

and have to be transported throughout this system,

can capture noradrenaline and then it can be secreted.

On the other hand, when we already have some protein here

that is no longer working and that begins to dysfunction,

we have to take it through the dynein,

so that in this part the lysosomes,

that we already saw in another class,

will degrade these proteins.

This system is also important

because if we we have an accident,

for example, an operation or anything else that happens

and the nerve is cut,

obviously, the part which is distal to the entire soma

is going to die, it is going to disappear completely.

It disappears into something called Wallerian degeneration process.

While the part that is attached to the soma

and all the protein synthesis,

can, not only be repaired, but to generate a new

terminal axon, and repair the nerve again.

The distal part does not regenerate, it has to die

because it doesn't even have the genes

nor the protein production systems,

while the proximal part is in charge of

regenerating the whole nerve

and it will also generate a dysfunction

in this nerve repair system,

many of the problems associated with cutting the nerves,

which we will see in other classes as well.

Now, we are in the terminal axon,

and what we are going to have is a series of vesicles

and mitochondrias

transported by the kinesin too.

These vesicles recapture or rather capture the neurotransmitter,

and there they accumulate it and when we activate our terminal axon

this vesicle is going to fuse with the membrane

and will allow the exit of the neurotransmitter,

that later will have its elimination mechanisms,

that we have already seen in the neurotransmitter classes.

Needless to say that it is imperative that there is some calcium

so that this vesicle knows

that it has to be merged with the membrane

and release the neurotransmitter to the synaptic space,

to the synaptic cleft in order to activate the post-synaptic neuron.

By studying these shapes

or these specializations of the neurons,

we have four main types of neurons

depending on its function.

We are going to have neurons that are monopolistic like this one,

in which, there's only one thing left from the soma, usually an axon

and the teledendrites.

We are going to have bipolar neurons, in which we have the soma

and we have two protuberances

that are formed in axons or dendrites.

We have the multipolares, which are among the most common,

especially in the central nervous system

and we have the pseudo-unipolar ones, in which one comes out,

but it divides itself in two.

Each one will have specialized functions.

For example, the unipolar

are closely associated to the processes of perception,

for example, on the retina, in the ear,

that we will see with the senses.

Many times, the bipolar neurons are interneuronal,

the multipolares are also used to communicate between many neurons

and the pseudo-unipolar are the ones we have seen

in the peripheral somatosensory systems

that transmit information

from the periphery to the spinal cord.

What is a synapse?

Since we understood more or less what is a neuron,

let's briefly see what a synapse is.

A synapse is basically the place where

a neuron communicates with another.

We have two special types of synapses,

electrical synapses and chemical synapses.

We already saw this in the class about cellular communication,

I'll only repeat it briefly.

The electrical synapse

is where communication takes place through electrical stimuli

that go through the cytoplasm from one cell to another

because both cytoplasms are connected through some tunnels

as the one that connects London and France

and these tunnels allow direct passage

of these potentials, of these ions

through the connexin protein.

Some important thing about this electrical synapse

is that it is bilateral,

what means ions can either pass from neuron A to neuron B,

and also from neuron B to neuron A.

Therefore, they are very good, especially in the heart,

for example, that they have to be turned on all at the same time

and as we already mentioned in the class of the electrical potential of the heart,

but they are not as good,

when you need a more important regulation

such as the central nervous system.

Now, if we we would to analyze it electrically,

we would put an electrode in our presynaptic neuron

and in our post-synaptic neuron,

we would see that depolarization, this electrical information

occurs practically immediately.

When the first one enters the potential for action,

the second one does it too, practically immediately

with a delay of less than milliseconds

and it can also be found in the potential for action,

thus generating a synchronized depolarization

and that makes all the neurons work at the same time

and this is because of the flow of potential.

This is especially important in the hypothalamus,

as we will see.

What is the problem or the limitations

does this this system have?

Since it is only a flow of ions,

they depend a lot on the distance that we have

between one cell and the other, they need to be attached, of course,

and also how much this flow is going to be separated.

For example, if we have a neuron

which transmits four ions,

by putting a completely arbitrary number,

and transmits four ions to another neuron that then bifurcates,

and these four ions go to separate paths.

The four ions could depolarize to this first neuron.

Here, we do generate a potential for action.

If we separate the second neuron,

these no longer reach the potential for action.

What have generated an activation in the first one,

won't generate an activation in the second.

This will also be important, as we'll see the next class,

I hope it will be in the next one,

the class about the axonic cone.

Just remember that when the distance is very long

or when we have to separate these potentials,

the amount of ions lowers, and therefore the potential,

and many times a stimulus that managed to depolarize something,

can be lost, dissipated

and that it is no longer generates that electric message.

Now, when we we have a--

We have already seen this. This is the hypothalamus.

The hypothalamus is the main source of electrical synapses,

even though there are many others.

For example, it is now known than in the motor system,

the electric synapse takes care of the movement.

That's what's interesting about what we will see later.

On the other hand, chemical synapses are, in quotes,

the most advanced ones.

They are more complicated than electrical synapses,

but we've seen them a lot already. It won't be difficult either.

When we measure its voltage

in the presynaptic and the post-synaptic neurons,

by depolarizing the first, we see a significant delay

in the depolarization of the second, of a few milliseconds.

This is because the ions flow, and depolarize the first neuron,

but as it is very separated, as we already saw it,

all of this potential energy dissipates,

these ions no longer can depolarize the second one.

To depolarize the second neuron,

we need the secretion of a neurotransmitter

and that it fits to their post-synaptic receptors,

as we have seen in the classes about neurotransmitters.

This delay between the first one being depolarized,

the neurotransmitter released and the second to be activated,

is this physiological delay of the synapse.

This is why chemical synapses are slower,

but they are also more efficient as they are modular.

We can better control how much they shoot.

As an example, electrical synapses

are the ones that insects have,

that's why they are so fast

and they react so quickly when we want to crush a fly

and it just flies away.

While our reflexes are much slower

because they are made of chemical synapses,

but again, we have more modulation and more control.

Now, what makes this chemical synapse

secrete this neurotransmitter?

We have seen it already in many of the classes.

We know that the neuron is activated, depolarized

and the vesicle merges into the membrane

and releases this specific neurotransmitter.

How do you do it?

Obviously, we need a specific stimulus,

for this vesicle, filled with the neurotransmitter,

to first capture the neurotransmitter and to be full,

and secondly, to be fused to the membrane

and to release it towards the synaptic cleft.

In the first case, all vesicles

depending on the neuron we are talking about,

have specific recapturing systems for the neurotransmitters.

To give you just an example,

there is a protein called BMAT,

that is in charge of filling the catecholamines

and the vesicles with, for example, noradrenaline.

Here we have this vesicle full of noradrenaline that is going to wait,

and wait and wait, and it will not be activated.

Suddenly, some lost vesicle that is connected

and it frees up a little bit of a neurotransmitter

before its time was up

and we call this a basal stimulation.

They are called micropotentials

and these micropotentials, if you put an electrode in them,

you will detect that, every hour, our new post-synaptic,

even though you don't do anything to it, it's suddenly going to turn on like this,

with a micropotential, once or twice,

you know that those lost vesicles

connect and release the neurotransmitter,

but, in general, these stimulations are very small.

Now, for us to have

a large quantity release of neurotransmitters

to the synaptic cleft

and therefore to activate enough receptors

to cause depolarization of the post-synaptic membrane,

we need to organize many vesicles.

How does the neuron

organizes all these vesicles?

It has very specific stimulus which are going to be called SNEAR proteins.

These SNEAR proteins

are going to be in these vesicles that we have already mentioned,

they are going to be connected to, for example, synaptobrevin,

and they are going to basically be like the chaperones,

they are going to take them by the hand.

So, when intracellular calcium increases,

for whatever reason,

this intracellular calcium connects to these SNEAR proteins.

It connects to, for example, synaptotagmine and synaptobrevin,

and they are going to take it by the hand to the cell membrane.

These SNARE proteins are going to generate a whole complex,

and what this complex will do is,

since we have the calcium, and the synaptotagmine

is going to take it to the membrane, this would be the membrane,

this would be our vesicle

and all these would be the SNARE proteins.

So when we have increased calcium,

that's going to be taken to the membrane,

this whole complex of SNARE proteins will merge,

both membranes are glued together,

that of the vesicle and that of the cell membrane,

and they're going to generate something that is called superpriming

and then it will be merged with the vesicle.

As if it was an egg, the shell of an egg,

they are going to open it, to break it and to fuse it with the vesicle 439 00:20:50,261 --> 00:20:53,599 to release its content towards the synaptic space.

More or less, you don't have to know this,

but five molecules of calcium are necessary

for each molecule or for each SNARE complex

to release the neurotransmitter.

Why is this important?

We have several diseases related to this set

or to this synapse,

among which, for your study,

I will only mention those that are related

in one of the most famous synapses,

the attachment of a motor neuron

with a muscle fiber, the neuromuscular junction.

Here we have, for example,

usually it would be,

once we activate our terminal axon

of the motor neuron,

we will have the voltage-dependent calcium channels.

When depolarization occurs,

calcium is going in through these channels

and all the vesicles that are close to the membrane

are going to merge and they will release the neurotransmitter.

Which is going to be attached to the acetylcholine receptors,

and to the nicotinic,

they are going to allow sodium to enter and the muscle contracts,

and we move what we want to move

because the acetylcholine came out and activated your receptor.

In the first example on how we can avoid

or how it can disrupt this connection, this synapse.

We have the famous botulinum toxin.

The botulinum toxin, what it basically does

is that it couples to these SNARE receptors,

which are the ones that merge the vesicles with the membrane

and prevent this vesicle to truly stick to the membrane

and release the neurotransmitter.

These vesicles that are completely unused

can no longer release the acetylcholine,

can no longer activate the acetylcholine receptor

and that muscle is paralyzed and flaccid,

it doesn't even have muscle tone,

because, as you recall the muscle contraction class,

for a muscle to have tone

we need to free the acetylcholine every so often.

When we add botulinum toxin into a muscle,

it becomes completely flaccid

and since the toxin lasts for months, up to six months,

the muscle remains completely flaccid for six months.

It is very bad when we ingest the botulinum toxin,

for example, from a soda bottle

and we go limp and die

with an intoxication or with botulism.

For example, when we we take the toxin

and we generate a medicine called botox,

we can block

the muscle we want.

This can be used for spasticity,

when a patient has a muscle that is too contracted

because of a stroke or cerebral palsy,

we can block it and make it more flaccid,

or it can also be used for aesthetic purposes.

Women normally used it,

but men apply it too,

to remove wrinkles, to prevent the muscle to become flaccid

and so that the skin is not with those stretch marks

or with those slits which can be ugly.

Not only that,

as the SNARE complex

is used for a large amount synapses,

the botulinum toxin has been used

to block all kinds of synapses.

Not only acetylcholine, but also glutamate, serotonin,

dopamine, etc.

So, it has also been used in painful pathologies.

If, instead of blocking the SNARE of the neuromuscular junction,

you block the glutamate in the spinal cord,

a patient, that is in severe pain

and nothing can lower it,

the pain will down after the application of the botulinum toxin.

Finally, when we are going to operate on someone

and that person needs to be paralyzed,

usually we don't use botulinum toxin,

but we can use other medications

that work in a similar way.

Another problem we may have is with two important diseases,

one is called myasthenia gravis,

this myasthenia gravis is an autoimmune disease.

We generate antibodies,

our immune system attacks our acetylcholine receptors

and as much as our motor neuron releases acetylcholine,

this cannot be connected to the acetylcholine receptor

and the muscle cannot be moved.

We are basically paralyzed by our immune system

due to the acetylcholine receptor.

On the other hand, other autoimmune disease

is the Lambert Eaton Syndrome.

This Lambert Eaton Syndrome

doesn't block the acetylcholine receptor

that is in the muscle,

but the calcium channel that would allow what we have already seen,

that those SNEAR proteins could attach and release the neurotransmitter

to the neuromuscular junction.

The Lambert Eaton Syndrome is blocked.

There is an antibody that blocks this calcium channel,

and by blocking the calcium channel,

we also block the fusion of the vesicles.

Here is the calcium channel.

We have blocked the fusion of the vesicles

and we can no longer secrete neurotransmitters,

but we have also generated a paralysis that can kill this person.

To review more about this topic,

I suggest you check out an Wikipedia article called Neuron.

It's very good, very complete.

And also Kandell, chapter two about nerve cells and behavior,

and the Basic Neurochemistry by Dr. Siegel's is very good too.

Here you can get much more information, for those interested.

Well, this was it for today's class.

As you know, any doubt, any comment,

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