Wellness">
Tema 01 - La Neurona
Tema 01 - La Neurona
Tema 01 - La Neurona
- quimioreceptores
(c.gustativos,c.carotideo)
- fotorreceptores (conos y
bastones retinianos)
FIGURE 2 Receptor morphology
and relationship to ganglion cells in
the somatosensory, auditory, and
visual systems. Receptors are
specialized structures that adopt
different shapes depending on their
function. In the somatosensory
system the receptor is a
specialized peripheral element that
is associated with the peripheral
process of a sensory neuron. In the
auditory and visual systems, a
distinct type of receptor cell is
present. In the auditory system, the
receptor (hair cell) synapses
directly on the ganglion cell,
whereas in the visual system, an
interneuron receives synapses
from the photoreceptor and in turn
synapses on the retinal ganglion
cell. Adapted from Bodian (1967).
Neuronas motoras
(1) - musculares
(2) - glandulares (ganglios vegetativos)
(3) - neurosecretoras (hipotalamo, epifisis)
3 1 2
Innervación Motora
NEURONAS DE INSECTOS
Destino del axón
De proyección
(principales).
Locales (interneuronas).
Citoplasma.
Función trófica. Muy abundante, gran
cantidad de orgánulos. Citoesqueleto muy
desarrollado.
Orgánulos membranosos
↑↑↑ RER, gran cantidad, grumos de Nissl,
↑↑↑ REL, lípidos. Almacenamiento regulado
de Ca2+ a lo largo de toda la célula. Muy
abundante en las dendritas.
↑↑↑ Golgi.
Vesículas de transporte,secreción y
sináptica.
Endosomas y lisosomas.
Peroxisomas (detoxificación)
↑↑ Muchas mitocondrias (requerimientos de
energía).
Citoesqueleto
Microtúbulos, microfilamentos de actina y
neurofilamentos (fil. Intermedios).
Determina morfología neuronal,
distribución de orgánulos, transporte
axónico.
Núcleo
Muy grande, esférico, casi todo
eucromatina.
Envoltura nuclear con muchos poros.
Uno o mas nucléolos de gran tamaño.
Nissl ag
n
nl olg
mg
nlo
olg
El núcleo
muestra diversas apariencias y estados
funcionales en los distintos tipos de
células nerviosas
(PML-ProMyelocytic Leukaemia)
Fig. 1.2.1. The pyramidal cell nucleus (N) with two nucleoli (arrows) and an
apical dendrite (D). Scale = 2 µm. (Mouse, neocortex.)
Núcleos de neuronas granulares
Las neuronas de los
granos son las
únicas que muestran
cromatina compacta
en forma de grumos
de heterocromatina
bajo la cubierta
nuclear
Fig. 1.9.3. The cerebellar synaptic glomeruli in the granular layer of the cerebellar cortex. Large mossy fiber
terminal (arrow) makes synapses with dendrites of granule cells (G). Scale = 2 µm. (Mouse, cerebellar
cortex.)
Cromatina
La cromatina neuronal tiene diferente
patrón de compactacion según la fase
maduración neuronal
Neuronas maduras
neurona inmadura (migrante)
Fig. 1.9.10. Precursor cells of nervous tissue from the wall of developing telencephalon. N - nucleus, P -
layer of developing dendrites and axons. Scale = 3 µm. (Chicken, embryonal telencephalon.)
Ubicación y
movimientos de
segmentos
cromosomicos a
zonas hetero- o eu-
cromatinicas
(a base de de-acetilacion y
metilacion para silenciar y de
hiperacetilacion para activar)
Fig. 2. Regulation of chromatin positioning and of transcriptional activity at specific nuclear regions. Sequence-specific transcription factors in conjunction with chromatin
remodeling and histone modifying complexes determine local chromatin structure and histone modifications (dark-green: condensed, silenced, hypoacetylated and other
“inactive” histone marks; red with Ac: decondensed, active, hyperacetylated and other “active” histone marks). Transcription factors also play an important role in
chromatin positioning and recent evidence suggests that radial chromatin positioning, interactions with the lamina, and differential associations with heterochromatic and
euchromatic nuclear areas might be determined by local chromatin structure and histone modifications and in particular by the patterns of histone acetylation (red and
green arrows pointing to the different nuclear regions and sub-structures). The patterns of histone acetylation of the corresponding different chromosomal domains are
inherited through mitosis (red and green banding pattern on mitotic chromosome) and this might provide a pathway for the re-establishment of chromatin arrangements
and radial nuclear order after mitosis (bottom, black arrows). Transcription factors are not evenly distributed in the nuclear space and transcriptional repressors (brown
dots) are enriched at the nuclear periphery (brown arrow), while transcriptional activators are enriched in areas containing transcription factories (yellow arrow). At the
nuclear periphery the enrichment in transcriptional repressors and histone deacetylase (HDAC)3-interacting with the nuclear lamina and associated INM proteins (grey Xs)
– might contribute to a reinforcement (left, black arrows) of histone marks, positioning, and silencing of chromatin residing in this area (silenced locus: dark-green dot,
perinuclear heterochromatin: light-green). Positioning of perinuclear chromatin might be also reinforced by direct interactions of hypoacetylated chromatin with the lamina
and INM proteins. At active nuclear regions (right) trans-acting and transcription factors associated with chromatin modifying complexes regulate interactions with other
structures involved in gene expression (top, black arrow), such as transcription factories (yellow) and nuclear pores (orange). In addition, gene loci (grey) also interact with
each other and such interactions can take place while loci are associated with other nuclear structures. Interaction with other components like nuclear pores and splicing
speckles (pink) might also help to coordinate transcription with pre-mRNA splicing and RNA export. The formation of transcription factories and of splicing speckles in the
nuclear interior might be driven by self-assembly on active chromatin and chromatin poised to be active harboring corresponding histone marks and localizing in the area
(black arrow, right, middle). Self-assembly on corresponding chromatin domains and other interactions with active chromatin/chromatin poised to be active might also
confine these domains to the active nuclear interior. Conversely, interactions with transcription factories and splicing speckles and other domains might stabilize and refine
chromatin positioning in this nuclear area and reinforce and refine local chromatin structure and histone modifications (black arrow, right, bottom). (Fedorova, 2008)
Nucleolo
El nucleolo es el lugar de congregacion de los "organizadores nucleolares“ (zonas de cromosomas con multiples copias de una
misma secuencia que codifica los RNA ribosomicos)
estructura transitoria en celulas mitoticas (desaparece durante la division celular) y muy desarrollada en neuronas
a) heterocromatina
perinucleolar
b) centros fibrilares (DNA):
homogeneos (transcribiendo)
y heterogeneos (con el DNA
plegado)
c) pars fibrilar (RNA)
d) pars granular (RNA)
e) + "nucleolo-esqueleto" y
sistemas enzimaticos
(nucleolina, AgNOR, SnuRP,
proteinas ribosomicas, etc.)
Fig. 1.2.8. The nucleolus of the Purkinje cell. Nucleolonema (red arrow) and perinucleolar
chromatin (blue arrow). Scale = 500 nm. (Mouse, cerebellar cortex.)
Nucleolo
heterocromatina
perinucleolar
Fibras de pericromatina
Granos de pericromatina
Nucleolo y cuerpo accesorio de Cajal ("coiled body")
compartimento receptor de los SMN nuevos (citoplasmicas “gemins”+snRNP+snRNA) o recicladas (de los
“speckles” o areas de splicing) (coilina p80, splicing snRNA, splicing snRNA factors)
c. de Cajal
coiled body
heterocromatina
perinucleolar
Fig. 1. The Spliceosomal U snRNP Cycle. Newly-synthesized spliceosomal U snRNAs (pink squares) are
exported to the cytoplasm where they are assembled into U snRNPs (red squares) by the SMN complex, which
also transports them into the nucleus and delivers them to the Cajal body. Further modifications of U snRNPs
and assembly of the tri-snRNP occurs in the Cajal body before the snRNPs are assembled into the
spliceosome in situ on newly-transcribed pre-mRNA in the perichromatin fibrils (PF) at the chromatin periphery.
Essential splicing factors are supplied by the splicing speckle, or interchromatin granule (ICG). After each
splicing step, UsnRNPs are re-cycled to the Cajal body for re-assembly and the spliced mRNA with attached
proteins (mRNP) is exported to the cytoplasm. The balls represent SMN (“1” = gemin1), gemins 2–8 and unrip.
The Sm ring is the U snRNA with seven Sm core proteins attached. Morris (2008) Biochimica et Biophysica
Acta 1783:2108–2115
Inclusiones nucleares: bastones intranucleares de Cajal
Fig. 1.2.7. Intranuclear rod (arrow) in pyramidal cell. The filamentous structure is apparent
in the inset. Scale = 1 µm. (Mouse, neocortex.)
Cuerpos PML (reguladores de transcripcion, SUMO-1 ubiquitina, clastosomas) (bastones Cajal, cuerpos
de Marinesco, …) (PML-ProMyelocytic Leukaemia)
La cubierta nuclear de neuronas:
Invaginacion nuclear, neurona de Purkinje
En neuronas muy
activas (en muchas
interneuronas) la
cubierta nuclear
aumenta su
superficie y se
generan pliegues o
invaginaciones
caracteristicas
Glia envolvente
alrededor de
neuronas
ganglionares con
citoplasma y
nucleo
voluminosos. El
nucleo solo con
eucromatina y
nucleolo
prominente
Fig. 1.3.5. Perikaryon of the unipolar nerve cell from the trigeminal ganglion. N - nucleus
of ganglion cell. Scale = 10 µm. (Rat, trigeminal ganglion.)
Citoplasma perinuclear: ribosomas y RER
El citoplasma
perinuclear
contiene cisternas
membranosas que
conforman los
grumos de Nissl
(RER) y el aparato
de Golgi
Fig. 1.2.2. The pyramidal cell nucleus (N) with an indentation (arrow). Scale = 1 µm. (Rat, hippocampus.)
Reticulo endoplasmico liso y rugoso
Funciones principales:
incorporacion y metabolismo lipidico
(detoxificacion, hepatocitos),
almacenamiento de iones (calcio, zinc),
movilizacion del glucogeno (hepatocitos,
hibernacion poiquilotermos)
Figure 12-34. Abundant smooth ER in a steroid-hormone-secreting cell. This Particularidades en neuronas
electron micrograph is of a testosterone-secreting Leydig cell in the human testis.
- Red tubular interna neuronal
(vacuolas y alojamiento
Figure 12-35. Three-
mitocondrial)
dimensional reconstruction - Cisternas submembranosas
of a region of the smooth (subsuperficiales)
and rough ER in a liver - Aparato de la espina
cell. The rough ER forms - Vesiculas de aporte
oriented stacks of flattened
cisternae, each having a
luminal space 20 to 30 nm
wide. The smooth ER
membrane is connected to
these cisternae and forms a
fine network of tubules 30 to
60 nm in diameter.
Cisternas sub-superficiales
Cisternas membranosas que se ubican debajo de
la membrana plasmatica
Pueden estar en comunicación con la cisterna
perinuclear, formar "pilas" y tener el lumen obliterado
(acumulan proteinas de adhesion?)
Fig. 1.1.2.12. Subsurface cisterns (empty arrows) in this cerebellar granule cell are
confluent with granular endoplasmic reticulum and its perinuclear cistern. N - nucleus,
large arrows - nuclear pores, A - astrocyte process. Scale = 100 nm. (Mouse,
cerebellum.)
Fig. 1.1.3.1. Golgi apparatus in the thalamocortical relay neuron. N - nucleus, Golgi
sacculi - red arrow, Golgi vesicles - blue arrow. Scale = 300 nm. (Rat, lateral geniculate
nucleus.)
Fig. 1.1.5.1. Multivesicular body (arrow). Note vesicles in its vicinity. Scale = 200
nm. (Rat, hippocampus.)
Endosoma Fig. 1.1.5.2. Multivesicular body. The tubular extension (arrow) connects the
multivesicular body to endosomal protein sorting compartments. Scale = 200 nm.
(Mouse, cerebellar cortex.)
Autofagosoma
Fig. 1.1.6.2. Secondary lysosome (red arrow) and peroxisomes with lamellar nucleoids
(blue arrows) in the pyramidal cell. N - nucleus. Scale = 400 nm. (Rat, hippocampus.)
Fig. 1.1.6.4. Cytosegrosome (asterisk) - an autolysosome containing focally
degenerating cytoplasm. Scale = 200 nm. (Human, neocortex.)
Grano de lipofuscina
Fig. 1.1.6.1. Secondary lysosome (L) in the histiocyte from injured trigeminal nerve. Fig. 1.1.6.3. Residual body (lipofuscin granule) in a pyramidal cell (arrow). Scale
Scale = 0.5 µm. (Rat, trigeminal nerve.) = 200 nm. (Rat, hippocampus.)
Finalmente el lisosoma acaba ocupado por residuos lipidicos no-hidrolizables, asi se generan los granos de lipofuscina
Citoesqueleto
Uniones celulares
Neuropilo
Dendritas
Superficie. Placas de receptores y
canales dependientes de
neurotransmisor (elementos
postsinápticos).
Porciones proximales. Igual al
soma.
Porciones distales. Citoesqueleto,
REL y mitocondrias (distribución
longitudinal). También ribosomas
libres (ramificación y base espinas).
Citoesqueleto. Organizados en
fascículos. ↑↑microtúbulos:
polaridad mixta( +-).
Neurofilamentos (menos que en
axones).
Espinas dendríticas.
Cabeza y cuello. Reciben sinapsis
excitadoras: 1 sinapsis por espina.
Red de actina.
La ultraestructura de dendritas es similar a la
del soma neuronal
ribosomas y grumos de Nissl (a veces debajo
de espinas)
Microtubulos abundantes (haz central)
(orientacion mezclada con extremos + y
extremos- hacia soma y hacia terminal)
menos neurofilamentos que en axones;
ciclosis alta (flujo axonico)
Corte transversal a dendrita de motoneurona (medula espinal) sobre la que se
establecen dos contactos sinapticos (observese la envoltura astrocitaria, As)
Figure 4-5. Scaled drawings of some characteristic neurons whose axons (A) and dendrites remain within the
central nervous system. (A) Neuron of inferior olivary nucleus. (B) Granule cell of cerebellar cortex. (C) Small cell
of reticular formation. (D) Small gelatinosa cell of spinal trigeminal nucleus. (E) Ovoid cell, nucleus of tractus
solitarius. (F) Large cell of reticular formation. (G) Spindle-shaped cell, substantia gelatinosa of spinal cord. (H),
Large cell of spinal trigeminal nucleus. (I) Neuron, putamen of lentiform nucleus. (J) Double pyramidal cell,
Ammon's horn of hippocampal cortex. (K) Cell from thalamic nucleus. (L) Cell from globus pallidus (Golgi
preparations, monkey). (Courtesy of the late Dr. Clement Fox, Wayne State University.)
La forma del árbol confiere propiedades de “resonancia“
La coincidencia temporal de potenciales postsinapticos en determinados puntos del
arbol permite la generacion de potenciales de accion (dendriticos y/o axonicos)
FIG. 4. Intracellular recording in alligator Purkinje cells. (A) Action potentials recorded in Purkinje cell dendrite 200 µm from
the surface. Successive hyperpolarizing current Injected through the recording electrode revealed that the large dendritic
spike shown on the first trace is actually produced by the addition of all-or-none components (arrows). This dendri tic spike
was generated by a dendritic EPSP produced by parallel fiber stimulation (upward arrow).'As the hyperpolarization is
increased, the different all-or-none depolarizing potentials are blocked In a sequential manner. (B) Reconstruction of the
Intradendritic action potential showing the six all-or-none components shown In (A). (C) Diagram of mechanism of dendritic
spike generation. Each all-or-none component is taken to be generated by a different hot spot (shown as a dark area) at or
near dendritic bifurcation. The action potential Is produced by the summation of all-or-none local responses that finally
reach the soma and generate a full outgoing action potential. (Modified from Llinas and Nicholson, 1971.)
Sitios de inicio del
potencial de accion
espinas en un axon
El citoesqueleto de las espinas son
microfilamentos (actina)
corte ultrafino criofractura
Corte longitudinal a dendrita de Purkinje mostrando varias espinas dendriticas; idem, criofractura
Frecuentemente, cada espina conecta con un solo boton presinaptico
En el interior de la espina se
distinguen:
Sinapsis excitadoras
Lizard cerebral cortex e inhibidoras sobre
espinas
Tipos de espinas
Los botones de las fibras musgosas son muy complejos; la reconstruccion de cortes
seriados permite contar mas de 70 contactos sinapticos sobre la/s espina/s ramificada
de una neurona piramidal
El potencial de accion que llegue a esa estructura provoca una liberacion simultanea de vesiculas
(neurortransmisores) y activacion de tantos canales ionicos que su accion es similar a una “detonacion”
Espina dendritica ramificada y botón musgoso (MFB)
Las cisternas membranosas, cuerpos multivesiculados y aparato de la espina suelen
acumular iones calcio en su interior; en la matriz hay abundantes protein quinasas
mvb
spine apparatus
Lizard cerebral cortex Raf-protein kinase immunoreactivity
From Mihaly et al. 1991
Espinas dendríticas en
situaciones patológicas
Situacion de reposo
Figure 4 Sinks and sources of Ca2+. Arrows show pathNvays of Ca2+ flux and the
associated numbers show the fraction of Ca2+ handled by a particular pathway. Of the
Ca2+ entering through Ca 2+-permeable channels, 95% binds to endogenous buffers
and 5% stays tree. Seventy percent of Ca2+ extrusion occurs directly across the plasma
Hirokawa membrane, whereas 30% passes through the S E R. A negligible fraction diffuses from
the spine head to the dendrite.
Una pequeña proporcion entra a la espina a traves de canales NMDA; la mayor cantidad de ellos se acumula en
cisternas del RE y son liberados o capturados según las circunstancias.
Transitorios de calcio en espinas
12-18 FIGURE 18 Calcium
transients can be imaged in
single dendritic spines in a rat
hippocampal slice. (A) Fluo-4, a
calcium-sensitive dye, injected
into a neuron enables an
individual spine to be imaged
under two-photon microscopy.
(B) An action potential (AP)
induces an increase in Ca2+ in
the dendrite and a larger
increase in the spine (averaged
responses). (C) Fluctuation
analysis indicated that spines
likely contain up to 20 voltage-
sensitive Ca channels; single
channel openings could be
detected, which had a high (0.5)
probability of opening following
a single action potential. From
Sabatini and Svoboda (2000).
Estimulacion electrica repetida: facilitacion sinaptica y
potenciacion del contacto
espina “normal”
Segmento inicial
Escasos ribosomas no Golgi, no RER . Mitocondrias, Haces de
MT y NF. Lámina submembranosa, red de material denso
(canales Na dep de volt). En ocasiones sinapsis inhibidoras
(candelabro).
Segmento intermedio:
Acaba lámina submembranosa, empieza vaina de mielina
(cuando hay). Nodos de Ranvier con densidad submembranosa.
Botones de paso. Vesículas membranosas (transporte).
Segmento distal:
Pierde vaina de mielina y forma botones sinápticos (terminales
axónicos)
Botones sinápticos de paso y terminales.
Membrana: alta densidad de canales iónicos dependientes de
voltaje.
Segmento inicial
tambien llamado "cono axonico“, diferente
del "cono de crecimiento axonico";
generalmente surge desde el soma, en otras
ocasiones surge de troncos dendriticos mas
o menos cercanos al soma;
excepcionalmente puede haber varios
"conos axonicos" y varios axones;
las "lineas" de union oligo-axon separan compartimentos axo-esqueleto reorganizado, cisternas membranosas y red densa
hermeticamente y favorecen la conduccion "saltatoria" de los submembranosa (nervio ciatico rata)
potenciales de accion (nervio optico)
bajo la
membrana
del nodo hay
abundante
material
denso.
El nodo es la
zona de
mayor
concentracion
de canales de
sodio
dependientes
de voltaje
(ankirina N).
Cortes transversales, zona internodal y
zona nodal
(los neurofilamentos se agrupan en la
zona nodal y se separan en la
internodal)
Bajo la membrana plasmatica de la
zona nodal hay engrosamiento
(ankirinas N que agrupan canales Na
dependientes de voltaje)
Segmento inicial
Segmento intermedio
Segmento terminal
Segmento terminal:
Botones de paso
periodicamente aprecen grupos de vesiculas
sinapticas y mitocondrias: botones de paso y
finalmente botones terminales (ambos son
elementos presinapticos); son estructuras
muy plasticas y adaptativas (estables si hay
funcionalidad, transitorios si no la hay) (se
establecen y/o retiran en minutos)
Segmento terminal:
boton presinaptico
se pierde mielina, aparecen vesiculas pequeñas
(sinapticas) y recubiertas (clatrina, endocitosis,
reciclamiento),
desciende el numero de neurofilamentos
se ramifica y origina botones presinapticos
(telodendria terminal)
desarrollo de redes de actina en las terminaciones
(especializacion presinaptica)
Conjunto de pequeñas vesiculas del elemento presinaptico que forman una poblacion relativamente autonoma
encargada de la liberacion controlada de moleculas "señal" (neurotransmisores)
Biogenesis: las primeras se forman en el aparato de Golgi, viajan por transporte anterogrado y se acumulan en el boton
presinaptico. Alli liberan neurotransmisor por exocitosis (mediada por Ca++ y potencial de accion), y se reciclan via
endocitosis (mediada por clatrina). Las vesiculas recien recicladas se recargan de neurotransmisor por transportadores
especificos (via antiporter con protones) (tienen una bomba de protones que les confiere un pH acido, aprox 5)
Numerosas proteinas de vesiculas sinapticas regulan su ciclo: acercamiento a un nuevo "sitio activo", "priming", nueva
exocitosis, etc.
Vesiculas: redondas, ovaladas, con nucleo denso