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1.
Brain Struct Funct ; 227(1): 361-379, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34665323

RESUMO

The basal ganglia and pontocerebellar systems regulate somesthetic-guided motor behaviors and receive prominent inputs from sensorimotor cortex. In addition, the claustrum and thalamus are forebrain subcortical structures that have connections with somatosensory and motor cortices. Our previous studies in rats have shown that primary and secondary somatosensory cortex (S1 and S2) send overlapping projections to the neostriatum and pontine nuclei, whereas, overlap of primary motor cortex (M1) and S1 was much weaker. In addition, we have shown that M1, but not S1, projects to the claustrum in rats. The goal of the current study was to compare these rodent projection patterns with connections in cats, a mammalian species that evolved in a separate phylogenetic superorder. Three different anterograde tracers were injected into the physiologically identified forepaw representations of M1, S1, and S2 in cats. Labeled fibers terminated throughout the ipsilateral striatum (caudate and putamen), claustrum, thalamus, and pontine nuclei. Digital reconstructions of tracer labeling allowed us to quantify both the normalized distribution of labeling in each subcortical area from each tracer injection, as well as the amount of tracer overlap. Surprisingly, in contrast to our previous findings in rodents, we observed M1 and S1 projections converging prominently in striatum and pons, whereas, S1 and S2 overlap was much weaker. Furthermore, whereas, rat S1 does not project to claustrum, we confirmed dense claustral inputs from S1 in cats. These findings suggest that the basal ganglia, claustrum, and pontocerebellar systems in rat and cat have evolved distinct patterns of sensorimotor cortical convergence.


Assuntos
Córtex Motor , Animais , Gatos , Claustrum , Neostriado , Vias Neurais , Filogenia , Ponte , Ratos , Córtex Somatossensorial , Tálamo
2.
J Neurophysiol ; 125(4): 1517-1531, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33689491

RESUMO

The rat whisker system connects the tactile environment with the somatosensory thalamocortical system using only two synaptic stages. Encoding properties of the first stage, the primary afferents with somas in the trigeminal ganglion (TG), has been well studied, whereas much less is known from the second stage, the brainstem trigeminal nuclei (TN). The TN are a computational hub giving rise to parallel ascending tactile pathways and receiving feedback from many brain sites. We asked the question, whether encoding properties of TG neurons are kept by two trigeminal nuclei, the principalis (Pr5) and the spinalis interpolaris (Sp5i), respectively giving rise to two "lemniscal" and two "nonlemniscal" pathways. Single units were recorded in anesthetized rats while a single whisker was deflected on a band-limited white noise trajectory. Using information theoretic methods and spike-triggered mixture models (STM), we found that both nuclei encode the stimulus locally in time, i.e., stimulus features more than 10 ms in the past do not significantly influence spike generation. They further encode stimulus kinematics in multiple, distinct response fields, indicating encoding characteristics beyond previously described directional responses. Compared with TG, Pr5 and Sp5i gave rise to lower spike and information rates, but information rate per spike was on par with TG. Importantly, both brainstem nuclei were found to largely keep encoding properties of primary afferents, i.e. local encoding and kinematic response fields. The preservation of encoding properties in channels assumed to serve different functions seems surprising. We discuss the possibility that it might reflect specific constraints of frictional whisker contact with object surfaces.NEW & NOTEWORTHY We studied two trigeminal nuclei containing the second neuron on the tactile pathway of whisker-related tactile information in rats. We found that the subnuclei, traditionally assumed to give rise to functional tactile channels, nevertheless transfer primary afferent information with quite similar properties in terms of integration time and kinematic profile. We discuss whether such commonality may be due the requirement to adapt to physical constraints of frictional whisker contact.


Assuntos
Fenômenos Eletrofisiológicos/fisiologia , Neurônios Aferentes/fisiologia , Percepção do Tato/fisiologia , Núcleos do Trigêmeo/fisiologia , Vibrissas/fisiologia , Vias Aferentes/fisiologia , Animais , Fenômenos Biomecânicos , Ratos , Fatores de Tempo
3.
Front Syst Neurosci ; 15: 813311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35153684

RESUMO

Rodents generate rhythmic whisking movements to explore their environment. Whisking trajectories, for one, appear as a fixed pattern of whisk cycles at 5-10 Hz driven by a brain stem central pattern generator. In contrast, whisking behavior is thought to be versatile and adaptable to behavioral goals. To begin to systematically investigate such behavioral adaptation, we established a whisking task, in which mice altered the trajectories of whisking in a goal-oriented fashion to gain rewards. Mice were trained to set the whisker to a defined starting position and generate a protraction movement across a virtual target (no touch-related tactile feedback). By ramping up target distance based on reward history, we observed that mice are able to generate highly specific whisking patterns suited to keep reward probability constant. On a sensorimotor level, the behavioral adaptation was realized by adjusting whisker kinematics: more distant locations were targeted using higher velocities (i.e., pointing to longer force generation), rather than by generating higher acceleration (i.e., pointing to stronger forces). We tested the suitability of the paradigm of tracking subtle alteration in whisking motor commands using small lesions in the rhythmic whisking subfield (RW) of the whisking-related primary motor cortex. Small contralateral RW lesions generated the deterioration of whisking kinematics with a latency of 12 days post-lesion, a change that was readily discriminated from changes in the behavioral adaptation by the paradigm.

4.
Nat Commun ; 9(1): 3907, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30254195

RESUMO

Sensory gating, where responses to stimuli during sensor motion are reduced in amplitude, is a hallmark of active sensing systems. In the rodent whisker system, sensory gating has been described only at the thalamic and cortical stages of sensory processing. However, does sensory gating originate at an even earlier synaptic level? Most importantly, is sensory gating under top-down or bottom-up control? To address these questions, we used an active touch task in behaving rodents while recording from the trigeminal sensory nuclei. First, we show that sensory gating occurs in the brainstem at the first synaptic level. Second, we demonstrate that sensory gating is pathway-specific, present in the lemniscal but not in the extralemniscal stream. Third, using cortical lesions resulting in the complete abolition of sensory gating, we demonstrate its cortical dependence. Fourth, we show accompanying decreases in whisking-related activity, which could be the putative gating signal.


Assuntos
Córtex Cerebral/fisiologia , Limiar Sensorial/fisiologia , Tato/fisiologia , Vibrissas/fisiologia , Animais , Tronco Encefálico/fisiologia , Feminino , Ratos Sprague-Dawley , Sinapses/fisiologia , Núcleos Talâmicos/fisiologia
5.
Nat Commun ; 9(1): 338, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29362373

RESUMO

Cortical computation is distributed across multiple areas of the cortex by networks of reciprocal connectivity. However, how such connectivity contributes to the communication between the connected areas is not clear. In this study, we examine the communication between sensory and motor cortices. We develop an eye movement task in mice and combine it with optogenetic suppression and two-photon calcium imaging techniques. We identify a small region in the secondary motor cortex (MOs) that controls eye movements and reciprocally connects with a rostrolateral part of the higher visual areas (VRL/A/AL). These two regions encode both motor signals and visual information; however, the information flow between the regions depends on the direction of the connectivity: motor information is conveyed preferentially from the MOs to the VRL/A/AL, and sensory information is transferred primarily in the opposite direction. We propose that reciprocal connectivity streamlines information flow, enhancing the computational capacity of a distributed network.


Assuntos
Córtex Cerebral/fisiologia , Movimentos Oculares/fisiologia , Córtex Motor/fisiologia , Rede Nervosa/fisiologia , Animais , Mapeamento Encefálico , Humanos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios Motores/fisiologia , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Células Receptoras Sensoriais/fisiologia , Córtex Somatossensorial/fisiologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-26483640

RESUMO

The primary (S1) and secondary (S2) somatosensory cortices project to several trigeminal sensory nuclei. One putative function of these corticofugal projections is the gating of sensory transmission through the trigeminal principal nucleus (Pr5), and some have proposed that S1 and S2 project differentially to the spinal trigeminal subnuclei, which have inhibitory circuits that could inhibit or disinhibit the output projections of Pr5. Very little, however, is known about the origin of sensorimotor corticofugal projections and their patterns of termination in the various trigeminal nuclei. We addressed this issue by injecting anterograde tracers in S1, S2 and primary motor (M1) cortices, and quantitatively characterizing the distribution of labeled terminals within the entire rostro-caudal chain of trigeminal sub-nuclei. We confirmed our anterograde tracing results by injecting retrograde tracers at various rostro-caudal levels within the trigeminal sensory nuclei to determine the position of retrogradely labeled cortical cells with respect to S1 barrel cortex. Our results demonstrate that S1 and S2 projections terminate in largely overlapping regions but show some significant differences. Whereas S1 projection terminals tend to cluster within the principal trigeminal (Pr5), caudal spinal trigeminal interpolaris (Sp5ic), and the dorsal spinal trigeminal caudalis (Sp5c), S2 projection terminals are distributed in a continuum across all trigeminal nuclei. Contrary to the view that sensory gating could be mediated by differential activation of inhibitory interconnections between the spinal trigeminal subnuclei, we observed that projections from S1 and S2 are largely overlapping in these subnuclei despite the differences noted earlier.


Assuntos
Técnicas de Rastreamento Neuroanatômico/métodos , Córtex Somatossensorial/anatomia & histologia , Núcleo Motor do Nervo Trigêmeo/anatomia & histologia , Núcleo Espinal do Trigêmeo/anatomia & histologia , Vibrissas/fisiologia , Animais , Feminino , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/fisiologia , Núcleo Motor do Nervo Trigêmeo/fisiologia , Núcleo Espinal do Trigêmeo/fisiologia
7.
J Neurophysiol ; 112(12): 3138-53, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25231609

RESUMO

The parietal reach region (PRR) and dorsal premotor cortex (PMd) form part of the fronto-parietal reach network. While neural selectivity profiles of single-cell activity in these areas can be remarkably similar, other data suggest that both areas serve different computational functions in visually guided reaching. Here we test the hypothesis that different neural functional organizations characterized by different neural synchronization patterns might be underlying the putatively different functional roles. We use cross-correlation analysis on single-unit activity (SUA) and multiunit activity (MUA) to determine the prevalence of synchronized neural ensembles within each area. First, we reliably find synchronization in PRR but not in PMd. Second, we demonstrate that synchronization in PRR is present in different cognitive states, including "idle" states prior to task-relevant instructions and without neural tuning. Third, we show that local field potentials (LFPs) in PRR but not PMd are characterized by an increased power and spike field coherence in the beta frequency range (12-30 Hz), further indicating stronger synchrony in PRR compared with PMd. Finally, we show that neurons with similar tuning properties tend to be correlated in their random spike rate fluctuations in PRR but not in PMd. Our data support the idea that PRR and PMd, despite striking similarity in single-cell tuning properties, are characterized by unequal local functional organization, which likely reflects different network architectures to support different functional roles within the fronto-parietal reach network.


Assuntos
Potenciais de Ação , Sincronização Cortical , Córtex Motor/fisiologia , Neurônios/fisiologia , Lobo Parietal/fisiologia , Desempenho Psicomotor/fisiologia , Animais , Ondas Encefálicas , Interpretação Estatística de Dados , Macaca mulatta , Masculino , Memória Espacial/fisiologia
8.
J Neurosci Methods ; 205(1): 72-85, 2012 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-22227443

RESUMO

Isolating action potentials of a single neuron (unit) is essential for intra-cortical neurophysiological recordings. Yet, during extracellular recordings in semi-chronic awake preparations, the relationship between neuronal soma and the recording electrode is typically not stationary. Neuronal waveforms often change in shape, and in the absence of counter-measures, merge with the background noise. To avoid this, experimenters can repeatedly re-adjust electrode positions to maintain the shapes of isolated spikes. In recordings with a larger number of electrodes, this process becomes extremely difficult. We report the performance of an automated algorithm that tracks neurons to obtain well isolated spiking, and autonomously adjusts electrode position to maintain good isolation. We tested the performance of this algorithm in isolating units with multiple individually adjustable micro-electrodes in a cortical surface area of macaque monkeys. We compared the performance in terms of signal quality and signal stability against passive placement of microelectrodes and against the performance of three human experts. The results show that our SpikeTrack2 algorithm achieves significantly better signal quality compared to passive placement. It is as least as good as humans in initially finding and isolating units, and better as the average and at least as good as the most proficient of three human experimenters in maintaining signal quality and signal stability. The autonomous tracking performance, the scalability of the system to large numbers of individual channels, and the possibility to objectify single unit recording criteria makes SpikeTrack2 a highly valuable tool for all multi-channel recording systems with individually adjustable electrodes.


Assuntos
Potenciais de Ação/fisiologia , Algoritmos , Córtex Cerebral/fisiologia , Fenômenos Eletrofisiológicos/fisiologia , Neurônios/fisiologia , Animais , Córtex Cerebral/citologia , Sistemas Inteligentes , Estimativa de Kaplan-Meier , Macaca mulatta , Masculino , Microeletrodos , Processamento de Sinais Assistido por Computador , Razão Sinal-Ruído
9.
Neuron ; 70(3): 536-48, 2011 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-21555078

RESUMO

In natural situations, movements are often directed toward locations different from that of the evoking sensory stimulus. Movement goals must then be inferred from the sensory cue based on rules. When there is uncertainty about the rule that applies for a given cue, planning a movement involves both choosing the relevant rule and computing the movement goal based on that rule. Under these conditions, it is not clear whether primates compute multiple movement goals based on all possible rules before choosing an action, or whether they first choose a rule and then only represent the movement goal associated with that rule. Supporting the former hypothesis, we show that neurons in the frontoparietal reach areas of monkeys simultaneously represent two different rule-based movement goals, which are biased by the monkeys' choice preferences. Apparently, primates choose between multiple behavioral options by weighing against each other the movement goals associated with each option.


Assuntos
Comportamento de Escolha/fisiologia , Sinais (Psicologia) , Objetivos , Movimento/fisiologia , Neurônios/fisiologia , Desempenho Psicomotor/fisiologia , Potenciais de Ação/fisiologia , Animais , Mapeamento Encefálico , Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Macaca mulatta , Masculino , Modelos Biológicos , Tempo de Reação/fisiologia , Percepção Espacial/fisiologia
10.
J Neurophysiol ; 102(3): 1632-46, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19535478

RESUMO

A growing body of evidence suggests that the barrel and septal regions in layer IV of rat primary somatosensory (SI) cortex may represent separate processing channels. To assess this view, pairs of barrel and septal neurons were recorded simultaneously in the anesthetized rat while a 4x4 array of 16 whiskers was mechanically stimulated at 4, 8, 12, and 16 Hz. Compared with barrel neurons, regular-spiking septal neurons displayed greater increases in response latencies as the frequency of whisker stimulation increased. Cross-correlation analysis indicated that the incidence and strength of neuronal coordination varied with the relative spatial configuration (within vs. across rows) and compartmental location (barrel vs. septa) of the recorded neurons. Barrel and septal neurons were strongly coordinated if both neurons were in close proximity and resided in the same row. Some barrel neurons were weakly coordinated, but only if they resided in the same row. By contrast, the strength of coordination among pairs of septal neurons did not vary with their spatial proximity or their spatial configuration within the arcs and rows of the barrel field. These differential responses provide further support for the view that the barrel and septal regions represent the cortical gateway for processing streams that encode specific aspects of the sensorimotor information associated with whisking behavior.


Assuntos
Potenciais de Ação/fisiologia , Neurônios/classificação , Neurônios/fisiologia , Septo do Cérebro/fisiologia , Córtex Somatossensorial/fisiologia , Vibrissas/inervação , Vias Aferentes/fisiologia , Animais , Biofísica , Masculino , Estimulação Física/métodos , Ratos , Ratos Sprague-Dawley , Septo do Cérebro/citologia , Córtex Somatossensorial/citologia , Estatística como Assunto , Fatores de Tempo
11.
J Neurophysiol ; 100(1): 50-63, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18450580

RESUMO

The whisker region in the rodent primary motor (MI) cortex receives dense projections from neurons aligned with the layer IV septa in the whisker region of the primary somatosensory (SI) cortex. To compare whisker-induced responses in MI with respect to the SI responses in the septa and adjoining barrel regions, we used several experimental approaches in anesthetized rats. Reversible inactivation of SI and the surrounding cortex suppressed the magnitude of whisker-induced responses in the MI whisker region by 80%. Subsequent laminar analysis of MI responses to electrical or mechanical stimulation of the whisker pad revealed that the most responsive MI neurons were located >or=1.0 mm below the pia. When layer IV neurons in SI were recorded simultaneously with deep MI neurons during low-frequency (2-Hz) deflections of the whiskers, the neurons in the SI barrels responded 2-6 ms earlier than those in MI. Barrel neurons displayed similar response latencies at all stimulus frequencies, but the response latencies in MI and the SI septa increased significantly when the whiskers were deflected at frequencies of 8 Hz. Finally, cross-correlation analysis of neuronal activity in SI and MI revealed greater amounts of time-locked coordination among septa-MI neuron pairs than among barrel-MI neuron pairs. These results suggest that the somatosensory corticocortical inputs to MI cortex convey information processed by the SI septal circuits.


Assuntos
Córtex Motor/citologia , Neurônios/fisiologia , Septo do Cérebro/citologia , Córtex Somatossensorial/citologia , Vibrissas/inervação , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Masculino , Ratos , Ratos Sprague-Dawley
12.
J Comp Neurol ; 499(1): 33-48, 2006 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16958106

RESUMO

In rodents, the whisker representation in primary somatosensory (SI) cortex projects to the dorsolateral neostriatum, but the location of these projections has never been characterized with respect to layer IV barrels and their intervening septa. To address this issue, we injected a retrograde tracer into the dorsolateral neostriatum and then reconstructed the location of the labeled corticostriatal neurons with respect to the cytochrome oxidase (CO)-labeled barrels in SI. When the tracer was restricted to a small focal site in the neostriatum, the retrogradely labeled neurons formed elongated strips that were parallel to the curvilinear orientation of layer IV barrel rows. After larger tracer injections, labeled neurons were distributed uniformly across layer V and were aligned with both the barrel and septal compartments. Labeled projections from the contralateral SI barrel cortex, however, were much fewer in number and were disproportionately associated with the septal compartments. A comparison of the labeling patterns in the ipsilateral and contralateral hemispheres revealed symmetric, mirror-image distributions that extended across primary motor cortex (MI) and multiple somatosensory cortical regions, including the secondary somatosensory (SII) cortex, the parietal ventral (PV) and parietal rhinal (PR) areas, and the posteromedial (PM) region. Examination of the thalamus revealed labeled neurons in the intralaminar nuclei, in the medial part of the posterior nucleus (POm), and in the ventrobasal complex. These results indicate that the dorsolateral neostriatum integrates sensorimotor information from multiple sensorimotor representations in the thalamus and cortex.


Assuntos
Mapeamento Encefálico , Córtex Motor/citologia , Neostriado/anatomia & histologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Córtex Somatossensorial/citologia , Animais , Biotina/análogos & derivados , Biotina/metabolismo , Toxina da Cólera/metabolismo , Dextranos/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Lateralidade Funcional , Masculino , Ratos , Ratos Sprague-Dawley , Estilbamidinas/metabolismo
13.
J Comp Neurol ; 498(5): 624-36, 2006 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-16917827

RESUMO

We have previously shown that projections from SI barrel cortex to the MI whisker representation originate primarily from columns of neurons that are aligned with the layer IV septa. SI barrel cortex also projects to SII cortex, but the origin of these projections has not been characterized with respect to the barrel and septal compartments. To address this issue, we injected retrograde tracers into the SII whisker representation and then reconstructed the location of the labeled neurons in SI with respect to the layer IV barrels. In some animals, two different tracers were injected into the whisker representations of SII and MI to detect double-labeled neurons that would indicate that some SI neurons project to both of these cortical areas. We found that the projections to SII cortex originate from sites that are uniformly distributed throughout the extragranular layers of barrel cortex. In cases in which different tracers were injected in SII and MI, double-labeled neurons appeared above and below the layer IV septal compartment and at sites aligned with the boundaries of the layer IV barrels. To the extent that the columns of neurons aligned with the barrel and septal compartments represent functionally distinct circuits, these results indicate that SII receives information from both circuits, whereas MI receives inputs primarily from the septal circuits.


Assuntos
Mapeamento Encefálico , Vias Eferentes/anatomia & histologia , Córtex Somatossensorial/fisiologia , Vibrissas/inervação , Amidinas/administração & dosagem , Amidinas/metabolismo , Animais , Benzofuranos/administração & dosagem , Benzofuranos/metabolismo , Biotina/administração & dosagem , Biotina/análogos & derivados , Biotina/metabolismo , Toxina da Cólera/administração & dosagem , Toxina da Cólera/metabolismo , Dextranos/administração & dosagem , Dextranos/metabolismo , Estimulação Elétrica/métodos , Iontoforese/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/citologia , Estilbamidinas/administração & dosagem , Estilbamidinas/metabolismo
14.
J Comp Neurol ; 480(3): 299-309, 2004 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-15515173

RESUMO

In rodents, each mystacial whisker is represented in the granular layer of primary somatosensory (SI) cortex by a compact cluster of cells known as a barrel, and barrels are separated from each other by domains that are called septa. Vertical columns of neurons aligned with each barrel act as a functional assembly to process information from a "principal" whisker, but a functional role has not been identified for vertical columns of neurons that are aligned with the septa. To determine whether these septal columns provide the main source of projections to primary motor (MI) cortex, we placed retrograde tracers in MI cortex and analyzed the location of the retrogradely labeled neurons with respect to the septal and barrel compartments of SI barrel cortex. In cases in which SI barrel cortex was sectioned tangentially, retrogradely labeled neurons in the extragranular layers of SI were plotted and superimposed onto reconstructions of the layer IV barrel field. In each of these cases, most labeled neurons were located above or below the septal regions of layer IV. When SI barrel cortex was sectioned coronally, we observed multiple columns of labeled SI neurons that were vertically aligned with the septal zones of layer IV. These results indicate that columns of neurons that are vertically aligned with the septa, or septal columns, are functionally linked by virtue of their projections to MI cortex. We hypothesize that these septal columns represent an interconnected and functionally distinct circuit that transmits information to MI and other brain regions involved in motor control.


Assuntos
Comportamento Animal/fisiologia , Córtex Motor/anatomia & histologia , Rede Nervosa/anatomia & histologia , Córtex Somatossensorial/anatomia & histologia , Vibrissas/inervação , Animais , Comportamento Exploratório/fisiologia , Masculino , Córtex Motor/fisiologia , Rede Nervosa/fisiologia , Vias Neurais/anatomia & histologia , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/fisiologia , Percepção Espacial/fisiologia
15.
Brain Res ; 1023(2): 231-42, 2004 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15374749

RESUMO

Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.


Assuntos
Gliose/fisiopatologia , Glicoproteínas de Membrana/deficiência , Degeneração Neural/etiologia , Neuroglia/fisiologia , Lipofuscinoses Ceroides Neuronais/fisiopatologia , Fatores Etários , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Astrócitos , Encéfalo/patologia , Antígeno CD11b/metabolismo , Calbindinas , Contagem de Células/métodos , Tamanho Celular , Sobrevivência Celular/fisiologia , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Interneurônios/metabolismo , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Chaperonas Moleculares/genética , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Lipofuscinoses Ceroides Neuronais/patologia , Parvalbuminas/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Somatostatina/metabolismo , Coloração e Rotulagem/métodos , Estatísticas não Paramétricas
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