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Apical dendritic spine density changes in vM1 layer 5 pyramidal neurons following facial nerve axotomy. (a) Two-dimensional computer-assisted trace of layer 5 pyramidal neuron from a representative mouse sacrificed 1 week after facial nerve lesion. The small rectangle indicates the area photographed in (b). (b) Representative microphotographs of second order dendritic spines from each experimental group. (c, d, e) Quantification of layer 5 pyramidal neurons spine density in 1st, 2nd, and 3rd order apical dendrites for each experimental group. Bars and error whiskers represent the mean + SEM. 1 W, 1 week after peripheral nerve lesion; 3 W, 3 weeks after peripheral nerve lesion; P<0.05∗.
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This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons,...
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... The facial nerve injury-induced changes have been found to reach well beyond electrophysiological and morphological changes in facial motoneurons and barrel somatosensory cortex. Actually, we have described significant facial axotomy-induced changes in vM1: persistent dendritic arborization retraction and persistent changes in electrophysiological properties of layer 5 pyramidal neurons (Urrego et al., 2011(Urrego et al., , 2015Múnera et al., 2012) and a transient increase microglial density (Cerón & Troncoso, 2016). Moreover, we also described that bilateral facial axotomy in rats impairs memory retrieval in hippocampal-dependent tasks, like object recognition memory (Moreno et al., 2010) and spatial memory (Patarroyo et al., 2017). ...
... circuit (Urrego et al., 2011(Urrego et al., , 2015Múnera et al., 2012). Since nucleus reuniens receives inputs from vM1 and trigeminal spinal nucleus (Krout et al., 2002;McKenna & Vertes, 2004) and projects densely to the whole dorsoventral extension of hippocampal CA1 region (Herkenham, 1978;Vertes et al., 2006), facial nerve axotomy may also explain the spine density changes observed in hippocampal pyramidal neurons. ...
... The selection of particular dendritic segments was based on the following criteria: (1) most Schaffer collateral axons project into the sr of CA1 (Ishizuka et al., 1990). Since we recently described a diminished long-term potentiation of hippocampal CA3-to-CA1 synapse associated to facial nerve injury (Torrado-Arévalo et al., 2021), we could expect changes in apical CA1 dendrites at sr associated with the facial nerve injury; (2) the medial entorhinal cortex (EC)(which receives motor cortex inputs) projects into slm of CA3 area; since we previously described facial axotomy-induced changes in the primary motor cortex (dendritic arborization retraction and changes in electrophysiological properties of layer 5 pyramidal neurons(Urrego et al., 2011(Urrego et al., , 2015Múnera et al., 2012)), we could expect changes in apical CA3 dendrites at slm related with facial nerve injury; and (3) basal dendrites for CA1 and CA3 areas were chosen for methodological simplicity: second-order dendrites at so are more isolated and displayed less crossing with neighboring dendrites that could interfere with the analysis. ...
Facial nerve injury in rats have been widely used to study functional and structural changes that occur in the injured motoneurons and other central nervous system structures related with sensorimotor processing. A decrease in long-term potentiation of hippocampal CA3-to-CA1 commissural synapse has recently been reported related to this peripheral injury. Additionally, it has been found increased corticosterone plasmatic levels, impairment in spatial memory consolidation, and hippocampal microglial activation in animals with facial nerve axotomy. In this work, we analyzed the neuronal morphology of hippocampal CA1 and CA3 pyramidal neurons in animals with either reversible or irreversible facial nerve injury. For this purpose, brain tissues of injured animals sacrificed at different postlesion times, were stained with the Golgi-Cox method and compared with control brains. It was found that both reversible and irreversible facial nerve injury-induced significant decreases in dendritic tree complexity, dendritic length, branch points, and spine density of hippocampal neurons. However, such changes' timing varied according to hippocampal area (CA1 vs. CA3), dendritic area (apical vs. basal), and lesion type (reversible vs. irreversible). In general, the observed changes were transient when animals had the possibility of motor recovery (reversible injury), but perdurable if the recovery from the lesion was impeded (irreversible injury). CA1 apical and CA3 basal dendritic tree morphology were more sensible to irreversible injury. It is concluded that facial nerve injury induced significant changes in hippocampal CA1 and CA3 pyramidal neurons morphology, which could be related to LTP impairments and microglial activation in the hippocampal formation, previously described.
... SPNs in the dorsolateral striatum were identified based on their morphological features as previously described (Bentea et al., 2020), e.g., either round or ovoid soma with a diameter ranging from 10 to 20µm that contains at least three primary dendrites having a relatively low density of spines that increases as the branching order becomes higher. Layer V pyramidal neurons in the motor cortex were identified as previously described (Urrego et al., 2015) based on morphological features, e.g., a triangular-shaped and relatively large soma that has the apical dendrites projecting toward the pial surface. Entire neurons within an imaging depth of stained sections (approximately 60 µm), excluding axons, were traced at 40× magnification. ...
Genetic variations resulting in the loss of function of the discs large homologs (DLG2)/postsynaptic density protein-93 (PSD-93) gene have been implicated in the increased risk for schizophrenia, intellectual disability, and autism spectrum disorders (ASDs). Previously, we have reported that mice lacking exon 14 of the Dlg2 gene (Dlg2-/-mice) display autistic-like behaviors, including social deficits and increased repetitive behaviors, as well as suppressed spontaneous excitatory postsynaptic currents in the striatum. However, the neural substrate underpinning such aberrant synaptic network activity remains unclear. Here, we found that the corticostriatal synaptic transmission was significantly impaired in Dlg2-/-mice, which did not seem attributed to defects in presynaptic releases of cortical neurons, but to the reduced number of functional synapses in the striatum, as manifested in the suppressed frequency of miniature excitatory postsynaptic currents in spiny projection neurons (SPNs). Using transmission electron microscopy, we found that both the density of postsynaptic densities and the fraction of perforated synapses were significantly decreased in the Dlg2-/-dorsolateral striatum. The density of dendritic spines was significantly reduced in striatal SPNs, but notably, not in the cortical pyramidal neurons of Dlg2-/-mice. Furthermore, a DLG2/PSD-93 deficiency resulted in the compensatory increases of DLG4/PSD-95 and decreases in the expression of TrkA in the striatum, but not particularly in the cortex. These results suggest that striatal dysfunction might play a role in the pathology of psychiatric disorders that are associated with a disruption of the Dlg2 gene.
... Consistent with the increased activity of astrocytes in pathophysiological states [45][46][47][48], an increased functionality of astrocytes (see circle size) in states other than the control state is apparent. Increased microglia interaction with PNs in the prefrontal cortex in psychiatric diseases [49,50] and other CNS disorders [51] has been reported. Consistent with these findings, we observed a subset of deep layer PNs (cluster 03) jointly participating with microglia in the disease state. ...
In psychiatric disorders, mismatches between disease states and therapeutic strategies are highly pronounced, largely because of unanswered questions regarding specific vulnerabilities of different cell types and therapeutic responses. Which cellular events (housekeeping or salient) are most affected? Which cell types succumb first to challenges, and which exhibit the strongest response to drugs? Are these events coordinated between cell types? How does disease and drug effect this coordination? To address these questions, we analyzed single-nucleus-RNAseq (sn-RNAseq) data from the human anterior cingulate cortex—a region involved in many psychiatric disorders. Density index, a metric for quantifying similarities and dissimilarities across functional profiles, was employed to identify common or salient functional themes across cell types. Cell-specific signatures were integrated with existing disease and drug-specific signatures to determine cell-type-specific vulnerabilities, druggabilities, and responsiveness. Clustering of functional profiles revealed cell types jointly participating in these events. SST and VIP interneurons were found to be most vulnerable, whereas pyramidal neurons were least. Overall, the disease state is superficial layer-centric, influences cell-specific salient themes, strongly impacts disinhibitory neurons, and influences astrocyte interaction with a subset of deep-layer pyramidal neurons. In absence of disease, drugs profiles largely recapitulate disease profiles, offering a possible explanation for drug side effects. However, in presence of disease, drug activities, are deep layer-centric and involve activating a distinct subset of deep-layer pyramidal neurons to circumvent the disease state’s disinhibitory circuit malfunction. These findings demonstrate a novel application of sn-RNAseq data to explain drug and disease action at a systems level.
... Hace unos años se constató que aparecen modificaciones morfológicas y electrofisiológicas en la corteza motora primaria de las vibrisas (Vibrisal Motor Cortex, vM1), cuando hay lesión del nervio facial (2,3). Asimismo, se caracterizó la activación de la microglía que circunda la corteza motora primaria de las vibrisas, asociada con dicha lesión (4). ...
... Si bien es conocido que el hipocampo no tiene conexión directa con las motoneuronas faciales lesionadas, se sabe que la corteza vM1 envía información al núcleo reuniens (33) y que este, a su vez, proyecta sobre las células piramidales de CA1 del hipocampo (34). Entonces, la pasividad inducida por la axotomía del nervio facial de las entradas táctiles de las vibrisas, puede causar un desequilibrio crítico en este sistema, no solo por la degradación de las entradas del trigémino a la vM1 y al núcleo reuniens, sino también, por la modificación fisiológica y estructural de las neuronas piramidales de la capa 5 de la vM1, como se ha observado en trabajos previos (2)(3)(4). ...
Introducción. Las lesiones del nervio facial afectan la plasticidad a largo plazo en el hipocampo, así como la memoria de reconocimiento de objetos y la memoria espacial, dos procesos dependientes de esta estructura.
Objetivo. Caracterizar en ratas el efecto de la lesión unilateral del nervio facial sobre la activación de células de la microglía en el hipocampo contralateral.
Materiales y métodos. Se hicieron experimentos de inmunohistoquímica para detectar células de la microglía en el hipocampo de ratas sometidas a lesión irreversible del nervio facial. Los animales se sacrificaron en distintos momentos después de la lesión, para evaluar la evolución de la proliferación (densidad de células) y la activación (área celular) de la microglía en el tejido del hipocampo. Los tejidos cerebrales de los animales de control se compararon con los de animales lesionados sacrificados en los días 1, 3, 7, 21 y 35 después de la lesión.
Resultados. Las células de la microglía en el hipocampo de animales con lesión del nervio facial mostraron signos de proliferación y activación a los 3, 7 y 21 días después de la lesión. Sin embargo, al cabo de cinco semanas, estas modificaciones se revirtieron, a pesar de que no hubo recuperación funcional de la parálisis facial.
Conclusiones. La lesión irreversible del nervio facial produce proliferación y activación temprana y transitoria de las células de la microglía en el hipocampo. Estos cambios podrían estar asociados con las modificaciones electrofisiológicas y las alteraciones comportamentales dependientes del hipocampo descritas recientemente.
... According to this, we suggest that the dendritic retraction observed in the present study could be a delayed effect of the high estradiol concentrations expressed during proestrus, an effect that cannot be modulated by progesterone because, unlike other brain regions, estrogens do not stimulate the expression of progesterone receptors (PR) in the cerebral cortex (Guennoun et al., 2015), and thus actin polymerization cannot be promoted by this hormone (Olbrich et al., 2013). In addition, it is also possible that dendritic retraction results from a reduction in neuronal excitability since it has been demonstrated that progesterone metabolites enhance the action of GABA, the main inhibitory neurotransmitter in the cortex (Smith et al., 1999) and, given that dendritic morphology is a critical factor for the establishment of synaptic contacts (Keil et al., 2017), dendritic retraction can cause an increase in the dendritic excitability of neurons of layer V of the motor cortex (Urrego et al., 2015) and changes in neuronal connectivity. ...
Many studies on neuronal plasticity have been conducted in the hippocampus and sensory cortices. In female rats in the estrus phase, when there is a low concentration of estradiol in the blood, there is a reduction in the dendritic spine density of CA1 neurons, while an increase in dendritic spines has been observed during metestrus, when progesterone levels are high. In comparison with the hippocampus, less information is known about dendritic remodeling of the motor cortex. Thus, the objective of the present study was to evaluate the neuronal morphology of pyramidal cells of layer V of the motor cortex in each phase of the estrous cycle. For this, we used Long-Evans strain rats and formed 4 experimental groups according to the phase of the estrous cycle at the moment of sacrifice: proestrus, estrus, metestrus, or diestrus. All animals were gently monitored regarding the expression of one estrous cycle in order to determine the regularity of the cycle. We obtained the brains in order to evaluate the neuronal morphology of neurons of layer V of the primary motor cortex following the Golgi-Cox method and Sholl analysis. Our results show that the dendritic arborization of neurons of rats sacrificed in the metestrus phase is reduced compared to the other phases of the estrous cycle. However, we did not find changes in dendritic spine density between experimental groups. When comparing our results with previous data, we can suggest that estrogens and progesterone differentially promote plasticity events in pyramidal neurons between different brain regions.
... In fact, the directions of interhemispheric differences in dendritic arborization complexity (Fig. 4) were consistent with the direction of the IDCD, especially in the arborization of the basal dendrites, which are more implicated in the integration of the neuronal response and have a strong effect on action potential output because of their direct attachment to the cell body and the proximity to the axon (Nevian et al., 2007;Zhou et al., 2008). The changes of dendritic arborization following SCI can be linked to the recently published observation depicting that axotomy of peripheral motor projections induce changes in the dendritic arborization of M1 pyramidal neurons in the rodent model submitted to a permanent lesion of the facial nerve (Urrego et al., 2015). In another recent study aiming at measuring the structural changes in the CNS of human patients suffering from degenerative pathology affecting interaction between cortical motoneurons and spinal motoneurons such as amyotrophic lateral sclerosis (ALS) or dementia, the authors observed a degeneration of the apical dendrites of pyramidal neurons located in Layer V of M1 (Betz's cells as described in the paper), to a larger extent in patients suffering from ALS (Genç et al., 2017). ...
Motor cortical areas from both hemispheres play a role during functional recovery after a unilateral spinal cord injury (SCI). However, little is known about the morphological and phenotypical differences that a SCI could trigger in corticospinal neurons of the ipsilesional and contralesional hemisphere. Using an SMI-32 antibody which specifically labeled pyramidal neurons in cortical layers V, we investigated the impact of a unilateral cervical cord lesion on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres of eight adult macaque monkeys compared with four intact control monkeys. We observed in F3 (but not in F6) interindividual variable and adaptive interhemispheric asymmetries of SMI-32 positive layer V neuronal density and dendritic arborization, which are strongly correlated with the extent of the SCI as well as the duration of functional recovery, but not with the extent (percentage) of functional recovery.
Significance statement
1. This study consists in a precise quantification on two different levels of the histological consequences on the long term of a traumatic and sudden unilateral interruption of the corticospinal tract at cervical level in 8 non-human primates (adult macaque monkeys).
2. The lesion affected the density and the morphology of layer v pyramidal neurons in the supplementary motor area (SMA), in the form of an interhemispheric adaptive asymmetry, correlated to the lesion size and duration of functional recovery.
3. These changes are reminiscent of those observed in SMA after unilateral lesion of the primary motor cortex, suggesting to some extent comparable mechanism of functional motor recovery from unilateral cortical or spinal lesion.
4. The dendritic arborization in the basal dendrites of the SMI-32 positive neurons in layer V showed a more prominent interhemispheric effect of the lesion than the apical dendrites.
... This dataset contains 3D-traced neurons from 6 distinct regions of the mouse neocortex. The regions with their cortical locations are visual-1 or primary visual (occipital) (Blackman et al. 2014;D'Souza et al. 2016;Risher et al. 2014;Falkner et al. 2016;Gerfen et al. 2018;Murase et al. 2016;Morgenstern et al. 2016;Lee et al. 2017;Longordo et al. 2013;Vannini et al. 2016;Gao et al. 2015), visual-2 or secondary visual (occipital) (Benavides-Piccione et al. 2005), prelimbic (prefrontal) (Routh et al. 2017;Gerfen et al. 2018), somato-1 or primary somatosensory (Ramos et al. 2008;Chen et al. 2009;Steger et al. 2013;Orner et al. 2014;Schierwagen et al. 2007;Alpár et al. 2003;Kimura and Murakami 2014;Gerfen et al. 2018), motor-1 or primary motor (frontal) (Gerfen et al. 2018;Economo et al. 2016;Urrego et al. 2015;Suter and Shepherd 2015), and motor-2 or secondary motor (frontal) (Benavides-Piccione et al. 2005;Gerfen et al. 2018). ...
Neuron shape and connectivity affect function. Modern imaging methods have proven successful at extracting morphological information. One potential path to achieve analysis of this morphology is through graph theory. Encoding by graphs enables the use of high throughput informatic methods to extract and infer brain function. However, the application of graph-theoretic methods to neuronal morphology comes with certain challenges in term of complex subgraph matching and the difficulty in computing intermediate shapes in between two imaged temporal samples. Here we report a novel, efficacious graph-theoretic method that rises to the challenges. The morphology of a neuron, which consists of its overall size, global shape, local branch patterns, and cell-specific biophysical properties, can vary significantly with the cell’s identity, location, as well as developmental and physiological state. Various algorithms have been developed to customize shape based statistical and graph related features for quantitative analysis of neuromorphology, followed by the classification of neuron cell types using the features. Unlike the classical feature extraction based methods from imaged or 3D reconstructed neurons, we propose a model based on the rooted path decomposition from the soma to the dendrites of a neuron and extract morphological features from each constituent path. We hypothesize that measuring the distance between two neurons can be realized by minimizing the cost of continuously morphing the set of all rooted paths of one neuron to another. To validate this claim, we first establish the correspondence of paths between two neurons using a modified Munkres algorithm. Next, an elastic deformation framework that employs the square root velocity function is established to perform the continuous morphing, which, as an added benefit, provides an effective visualization tool. We experimentally show the efficacy of NeuroPath2Path, NeuroP2P, over the state of the art.
... Importantly, these reductions were observed primarily in the outer molecular layer where denervation had occurred. Additionally, deafness or facial nerve lesions resulted in pathwayspecific reductions in dendritic morphology, in either primary auditory cortex ( Bose et al., 2010), or primary motor cortex pyramidal cells ( Urrego et al., 2015), respectively. The attenuated responses of SC stimulation we report, along with the reported reduction in CA3 pyramidal excitability (Condomitti et al., 2018), could lead to reduced SC output. ...
G-protein-coupled receptor 158 (Gpr158) is highly expressed in striatum, hippocampus and prefrontal cortex. It gained attention as it was implicated in physiological responses to stress and depression. Recently, Gpr158 has been shown to act as a pathway-specific synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure, and function. Although rodent Gpr158 expression is highest in CA3, considerable expression occurs in CA1 especially after the first postnatal month. Here, we combined hippocampal-dependent behavioral paradigms with subsequent electrophysiological and morphological analyses from the same group of mice to assess the effects of Gpr158 deficiency on CA1 physiology and function. We demonstrate deficits in spatial memory acquisition and retrieval in the Morris water maze paradigm, along with deficits in the acquisition of extinction memory in the passive avoidance test in Gpr158 KO mice. Electrophysiological recordings from CA1 pyramidal neurons revealed normal basal excitatory and inhibitory synaptic transmission, however, Schaffer collateral stimulation yielded dramatically reduced post-synaptic currents. Interestingly, intrinsic excitability of CA1 pyramidals was found increased, potentially acting as a compensatory mechanism to the reductions in Schaffer collateral-mediated drive. Both ex vivo and in vitro, neurons deficient for or with lowered levels of Gpr158 exhibited robust reductions in dendritic architecture and complexity, i.e., reduced length, surface, bifurcations, and branching. This effect was localized in the apical but not basal dendrites of adult CA1 pyramidals, indicative of compartment-specific alterations. A significant positive correlation between spatial memory acquisition and extent of complexity of CA1 pyramidals was found. Taken together, we provide first evidence of significant disruptions in hippocampal CA1 neuronal dendritic architecture and physiology, driven by Gpr158 deficiency. Importantly, the hippocampal neuronal morphology deficits appear to support the impairments in spatial memory acquisition observed in Gpr158 KO mice.
... Importantly, these reductions were observed primarily in the outer molecular layer where denervation had occurred. Additionally, deafness or facial nerve lesions resulted in pathway-specific reductions in dendritic morphology, in either primary auditory cortex (Bose et al., 2010), or primary motor cortex pyramidal cells (Urrego et al., 2015), respectively. The attenuated responses of SC stimulation we report, along with the reported reduction in CA3 pyramidal excitability (Condomitti et al., 2018), could lead to reduced SC output. ...
G-protein-coupled receptor 158 (Gpr158) is highly expressed in striatum, hippocampus and prefrontal cortex. It gained attention as it was implicated in physiological responses to stress and depression. Recently, Gpr158 has been shown to act as a pathway-specific synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure, and function. Although rodent Gpr158 expression is highest in CA3, considerable expression occurs in CA1 especially after the first postnatal month. Here, we combined hippocampal-dependent behavioral paradigms with subsequent electrophysiological and morphological analyses from the same group of mice to assess the effects of Gpr158 deficiency on CA1 physiology and function. We demonstrate deficits in spatial memory acquisition and retrieval in the Morris water maze paradigm, along with deficits in the acquisition of extinction memory in the passive avoidance test in Gpr158 KO mice. Electrophysiological recordings from CA1 pyramidal neurons revealed normal basal excitatory and inhibitory synaptic transmission, however, Schaffer collateral stimulation yielded dramatically reduced post-synaptic currents. Interestingly, intrinsic excitability of CA1 pyramidals was found increased, potentially acting as a compensatory mechanism to the reductions in Schaffer collateral-mediated drive. Both ex vivo and in vitro, neurons deficient for Gpr158 exhibited robust reductions in dendritic architecture and complexity, i.e., reduced length, surface, bifurcations, and branching. This effect was localized in the apical but not basal compartment of adult CA1 pyramidals, indicative of pathway-specific alterations. A significant positive correlation between spatial memory acquisition and extent of complexity of CA1 pyramidals was found. Taken together, we provide first evidence of significant disruptions in hippocampal CA1 neuronal dendritic architecture and physiology, driven by Gpr158 deficiency. Importantly, the hippocampal neuronal morphology deficits appear to support the impairments in spatial memory acquisition observed in Gpr158 KO mice.
... Mientras que el acortamiento de las dendritas apical es tardía y transitoria (ya que sólo se ha observado a las tres semanas post-lesión). Más aún, las espinas dendríticas (que son los sitios específicos de contacto sináptico con otra neurona) también se ven afectadas: disminuyen su número desde los primeros días luego de la lesión (Urrego et al., 2015). ...
... El desequilibrio de las entradas sensoriales por la inmovilización de las vibrisas y la pérdida de dianas sinápticas sobre las motoneuronas faciales podrían explicar las modificaciones diferenciales en la retracción de los árboles dendríticos basales y apicales. La retracción inicial de las ramificaciones apicales de las neuronas de la corteza motora primaria podría estar relacionada con una disminución de las entradas sensoriales procedentes de la corteza somatosensorial, cuyas neuronas de proyección córtico-cortical se ha demostrado que sufren modificaciones estructurales y funcionales con tratamientos que deterioran la entrada sensorial (Urrego et al., 2015). ...
... De modo que la detección, cuantificación y evaluación morfológica es relativamente fácil en estas células fluorescentes. Las lesiones del nervio facial en estos ratones transgénicos nos ha permitido describir un aumento significativo en el número de células microgliales en la corteza motora primaria luego de la lesión (Urrego et al., 2015). Más aún, las células microgliales no sólo aumentan en número, sino que muestran un fenotipo de activación muy temprano (de tres a siete días post-lesión) y transitorio. ...
p>Desde hace algunos años el grupo de investigación de Neurofisiología Comportamental de la Universidad Nacional de Colombia ha venido evaluando los cambios que ocurren en el sistema nervioso central luego de la lesión de un nervio periférico. Específicamente trabajamos con el modelo de lesión del nervio facial en roedores para evaluar las modificaciones funcionales y estructurales que ocurren en la corteza sensoriomotora primaria luego de la lesión. Al lesionarse el nervio facial, el cerebro entra en un programa de reorganización que incluye cambios electrofisiológicos en las neuronas de la corteza motora que comandan los movimientos faciales (M1). En este sentido, las células de la corteza motora cerebral se vuelven más excitables y modifican su respuesta ante estímulos sensoriales. La reorganización tras la lesión también incluye cambios morfológicos en M1: las células piramidales de la corteza motora retraen su árbol dendrítico y disminuye la densidad de sus espinas dendríticas. En asociación con estos cambios, las células de M1 disminuyen transitoriamente su inmunorreactividad para NeuN (marcador específico de núcleos neuronales) y aumentan la expresión de GAP43 (proteína de crecimiento axonal). Esto indica, posiblemente, un cambio metabólico celular en asociación con la búsqueda de nuevas dianas sinápticas. Finalmente, hallamos que la glía circundante en M1 (tanto astrocitos como microglía) se activa de manera muy temprana luego de lesiones del nervio facial. Esto podría indicar que el remodelamiento estructural y funcional hallado en las neuronas corticales es el resultado de la interacción entre la activación de la glía circundante y las células piramidales de M1 (aunque se necesitan muchos experimentos adicionales que así lo demuestren).
Abstract
Our research group (Neurofisiología Comportamental, Universidad Nacional de Colombia) has evaluated changes in the central nervous system induced by peripheral nerve injuries. We have characterized facial nerve lesion-induced structural and functional changes in primary motor cortex pyramidal neurons (M1) in rodents. Following the lesion, M1 neurons modified their spontaneous basal firing frequency: they become more excitable. Moreover, we found changes in evoked-activity with somatosensory stimulation after facial nerve lesion. Morphologically, it was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of M1 pyramidal neurons. Dendritic branching of the pyramidal cells underwent overall shrinkage and dendrites suffered transient spine pruning. Additionally, we evaluated the reorganization processes in the central nervous system by using both neuronal and glial markers. Decreased NeuN (neuronal nuclei antigen) immunoreactivity and increased GAP-43 (growth-associated protein 43) immunoreactivity were found M1 after facial nerve lesion. In addition, we also observed astrogliosis and microglial activation sourrounding M1 early after facial nerve injury. Taken together these findings suggest that facial nerve lesions induce widespread reorganization in M1 including neuronal shrinkage, axon sprouting as well as astrocytic and microglia activation. These results suggest that facial nerve injuries elicit active remodeling due to pyramidal neuron and glia interaction (although additional experiments that demonstrate it are needed)</p
