RESUMO
The neocortex and striatum are topographically organized for sensory and motor functions. While sensory and motor areas are lateralized for touch and motor control, respectively, frontal areas are involved in decision-making, where lateralization of function may be less important. This study contrasted the topographic precision of cell-type-specific ipsilateral and contralateral cortical projections while varying the injection site location in transgenic mice of both sexes. While sensory cortical areas had strongly topographic outputs to the ipsilateral cortex and striatum, they were weaker and not as topographically precise to contralateral targets. The motor cortex had somewhat stronger projections but still relatively weak contralateral topography. In contrast, frontal cortical areas had high degrees of topographic similarity for both ipsilateral and contralateral projections to the cortex and striatum. Corticothalamic organization is mainly ipsilateral, with weaker, more medial contralateral projections. Corticostriatal computations might integrate input outside closed basal ganglia loops using contralateral projections, enabling the two hemispheres to act as a unit to converge on one result in motor planning and decision-making.
Assuntos
Lobo Frontal , Camundongos Transgênicos , Córtex Motor , Vias Neurais , Córtex Somatossensorial , Animais , Córtex Motor/fisiologia , Masculino , Feminino , Camundongos , Córtex Somatossensorial/fisiologia , Lobo Frontal/fisiologia , Vias Neurais/fisiologia , Lateralidade Funcional/fisiologia , Corpo Estriado/fisiologiaRESUMO
Intracortical inhibition in motor cortex (M1) regulates movement and motor learning. If cortical and thalamic inputs target different inhibitory cell types in different layers, then these afferents may play different roles in regulating M1 output. Using mice of both sexes, we quantified input to two main classes of M1 interneurons, parvalbumin+ (PV+) cells and somatostatin+ (SOM+) cells, using monosynaptic rabies tracing. We then compared anatomic and functional connectivity based on synaptic strength from sensory cortex and thalamus. Functionally, each input innervated M1 interneurons with a unique laminar profile. Different interneuron types were excited in a distinct, complementary manner, suggesting feedforward inhibition proceeds selectively via distinct circuits. Specifically, somatosensory cortex (S1) inputs primarily targeted PV+ neurons in upper layers (L2/3) but SOM+ neurons in middle layers (L5). Somatosensory thalamus [posterior nucleus (PO)] inputs targeted PV+ neurons in middle layers (L5). In contrast to sensory cortical areas, thalamic input to SOM+ neurons was equivalent to that of PV+ neurons. Thus, long-range excitatory inputs target inhibitory neurons in an area and a cell type-specific manner, which contrasts with input to neighboring pyramidal cells. In contrast to feedforward inhibition providing generic inhibitory tone in cortex, circuits are selectively organized to recruit inhibition matched to incoming excitatory circuits.SIGNIFICANCE STATEMENT M1 integrates sensory information and frontal cortical inputs to plan and control movements. Although inputs to excitatory cells are described, the synaptic circuits by which these inputs drive specific types of M1 interneurons are unknown. Anatomical results with rabies tracing and physiological quantification of synaptic strength shows that two main classes of inhibitory cells (PV+ and SOM+ interneurons) both receive substantial cortical and thalamic input, in contrast to interneurons in sensory areas (where thalamic input strongly prefers PV+ interneurons). Further, each input studied targets PV+ and SOM+ interneurons in a different fashion, suggesting that separate, specific circuits exist for recruitment of feedforward inhibition.
Assuntos
Córtex Motor , Raiva , Feminino , Masculino , Camundongos , Animais , Parvalbuminas/metabolismo , Córtex Motor/metabolismo , Raiva/metabolismo , Tálamo/fisiologia , Neurônios/fisiologia , Interneurônios/fisiologia , Somatostatina/metabolismoRESUMO
Within the basal ganglia circuit, the external globus pallidus (GPe) is critically involved in motor control. Aside from Foxp2+ neurons and ChAT+ neurons that have been established as unique neuron types, there is little consensus on the classification of GPe neurons. Properties of the remaining neuron types are poorly defined. In this study, we leverage new mouse lines, viral tools, and molecular markers to better define GPe neuron subtypes. We found that Sox6 represents a novel, defining marker for GPe neuron subtypes. Lhx6+ neurons that lack the expression of Sox6 were devoid of both parvalbumin and Npas1. This result confirms previous assertions of the existence of a unique Lhx6+ population. Neurons that arise from the Dbx1+ lineage were similarly abundant in the GPe and displayed a heterogeneous makeup. Importantly, tracing experiments revealed that Npas1+-Nkx2.1+ neurons represent the principal noncholinergic, cortically-projecting neurons. In other words, they form the pallido-cortical arm of the cortico-pallido-cortical loop. Our data further show that pyramidal-tract neurons in the cortex collateralized within the GPe, forming a closed-loop system between the two brain structures. Overall, our findings reconcile some of the discrepancies that arose from differences in techniques or the reliance on preexisting tools. Although spatial distribution and electrophysiological properties of GPe neurons reaffirm the diversification of GPe subtypes, statistical analyses strongly support the notion that these neuron subtypes can be categorized under the two principal neuron classes: PV+ neurons and Npas1+ neurons.SIGNIFICANCE STATEMENT The poor understanding of the neuronal composition in the external globus pallidus (GPe) undermines our ability to interrogate its precise behavioral and disease involvements. In this study, 12 different genetic crosses were used, hundreds of neurons were electrophysiologically characterized, and >100,000 neurons were histologically- and/or anatomically-profiled. Our current study further establishes the segregation of GPe neuron classes and illustrates the complexity of GPe neurons in adult mice. Our results support the idea that Npas1+-Nkx2.1+ neurons are a distinct GPe neuron subclass. By providing a detailed analysis of the organization of the cortico-pallidal-cortical projection, our findings establish the cellular and circuit substrates that can be important for motor function and dysfunction.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Córtex Cerebral/metabolismo , Globo Pálido/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Fator Nuclear 1 de Tireoide/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Vias Neurais/metabolismo , Fator Nuclear 1 de Tireoide/genéticaRESUMO
We describe an engineered family of highly antigenic molecules based on GFP-like fluorescent proteins. These molecules contain numerous copies of peptide epitopes and simultaneously bind IgG antibodies at each location. These 'spaghetti monster' fluorescent proteins (smFPs) distributed well in neurons, notably into small dendrites, spines and axons. smFP immunolabeling localized weakly expressed proteins not well resolved with traditional epitope tags. By varying epitope and scaffold, we generated a diverse family of mutually orthogonal antigens. In cultured neurons and mouse and fly brains, smFP probes allowed robust, orthogonal multicolor visualization of proteins, cell populations and neuropil. smFP variants complement existing tracers and greatly increase the number of simultaneous imaging channels, and they performed well in advanced preparations such as array tomography, super-resolution fluorescence imaging and electron microscopy. In living cells, the probes improved single-molecule image tracking and increased yield for RNA-seq. These probes facilitate new experiments in connectomics, transcriptomics and protein localization.
Assuntos
Proteínas Luminescentes/química , Microscopia Eletrônica/métodos , Microscopia de Fluorescência/métodos , Animais , Antígenos , Mapeamento Encefálico , Drosophila , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Neurônios , Conformação ProteicaRESUMO
Cortical cells integrate synaptic input from multiple sources, but how these different inputs are distributed across individual neurons is largely unknown. Differences in input might account for diverse responses in neighboring neurons during behavior. We present a strategy for comparing the strengths of multiple types of input onto the same neuron. We developed methods for independent dual-channel photostimulation of synaptic inputs using ChR2 together with ReaChR, a red-shifted channelrhodopsin. We used dual-channel photostimulation to probe convergence of sensory information in the mouse primary motor cortex. Input from somatosensory cortex and thalamus converges in individual neurons. Similarly, inputs from distinct somatotopic regions of the somatosensory cortex are integrated at the level of single motor cortex neurons. We next developed a ReaChR transgenic mouse under the control of both Flp- and Cre-recombinases that is an effective tool for circuit mapping. Our approach to dual-channel photostimulation enables quantitative comparison of the strengths of multiple pathways across all length scales of the brain.
Assuntos
Mapeamento Encefálico , Córtex Motor/citologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Córtex Somatossensorial/fisiologia , Animais , Animais Recém-Nascidos , Channelrhodopsins , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Técnicas In Vitro , Luz , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Piperazinas/farmacologia , Quinoxalinas/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Transdução GenéticaRESUMO
Cortical neurons form specific circuits, but the functional structure of this microarchitecture and its relation to behaviour are poorly understood. Two-photon calcium imaging can monitor activity of spatially defined neuronal ensembles in the mammalian cortex. Here we applied this technique to the motor cortex of mice performing a choice behaviour. Head-fixed mice were trained to lick in response to one of two odours, and to withhold licking for the other odour. Mice routinely showed significant learning within the first behavioural session and across sessions. Microstimulation and trans-synaptic tracing identified two non-overlapping candidate tongue motor cortical areas. Inactivating either area impaired voluntary licking. Imaging in layer 2/3 showed neurons with diverse response types in both areas. Activity in approximately half of the imaged neurons distinguished trial types associated with different actions. Many neurons showed modulation coinciding with or preceding the action, consistent with their involvement in motor control. Neurons with different response types were spatially intermingled. Nearby neurons (within approximately 150 mum) showed pronounced coincident activity. These temporal correlations increased with learning within and across behavioural sessions, specifically for neuron pairs with similar response types. We propose that correlated activity in specific ensembles of functionally related neurons is a signature of learning-related circuit plasticity. Our findings reveal a fine-scale and dynamic organization of the frontal cortex that probably underlies flexible behaviour.
Assuntos
Comportamento Animal/fisiologia , Aprendizagem/fisiologia , Córtex Motor/citologia , Córtex Motor/fisiologia , Vias Neurais/fisiologia , Animais , Transporte Axonal , Comportamento de Escolha/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Motores/fisiologia , Odorantes/análise , Células Piramidais/fisiologia , Recompensa , Estimulação Química , Fatores de Tempo , Língua/citologia , Língua/inervação , Língua/fisiologiaRESUMO
Mouse visual cortex is subdivided into multiple distinct, hierarchically organized areas that are interconnected through feedforward (FF) and feedback (FB) pathways. The principal synaptic targets of FF and FB axons that reciprocally interconnect primary visual cortex (V1) with the higher lateromedial extrastriate area (LM) are pyramidal cells (Pyr) and parvalbumin (PV)-expressing GABAergic interneurons. Recordings in slices of mouse visual cortex have shown that layer 2/3 Pyr cells receive excitatory monosynaptic FF and FB inputs, which are opposed by disynaptic inhibition. Most notably, inhibition is stronger in the FF than FB pathway, suggesting pathway-specific organization of feedforward inhibition (FFI). To explore the hypothesis that this difference is due to diverse pathway-specific strengths of the inputs to PV neurons we have performed subcellular Channelrhodopsin-2-assisted circuit mapping in slices of mouse visual cortex. Whole-cell patch-clamp recordings were obtained from retrobead-labeled FF(V1âLM)- and FB(LMâV1)-projecting Pyr cells, as well as from tdTomato-expressing PV neurons. The results show that the FF(V1âLM) pathway provides on average 3.7-fold stronger depolarizing input to layer 2/3 inhibitory PV neurons than to neighboring excitatory Pyr cells. In the FB(LMâV1) pathway, depolarizing inputs to layer 2/3 PV neurons and Pyr cells were balanced. Balanced inputs were also found in the FF(V1âLM) pathway to layer 5 PV neurons and Pyr cells, whereas FB(LMâV1) inputs to layer 5 were biased toward Pyr cells. The findings indicate that FFI in FF(V1âLM) and FB(LMâV1) circuits are organized in a pathway- and lamina-specific fashion.
Assuntos
Retroalimentação Fisiológica/fisiologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vias Neurais/fisiologia , Técnicas de Cultura de Órgãos , Estimulação Luminosa/métodosRESUMO
Determining how long-range synaptic inputs engage pyramidal neurons in primary motor cortex (M1) is important for understanding circuit mechanisms involved in regulating movement. We used channelrhodopsin-2-assisted circuit mapping to characterize the long-range excitatory synaptic connections made by multiple cortical and thalamic areas onto pyramidal neurons in mouse vibrissal motor cortex (vM1). Each projection innervated vM1 pyramidal neurons with a unique laminar profile. Collectively, the profiles for different sources of input partially overlapped and spanned all cortical layers. Specifically, orbital cortex (OC) inputs primarily targeted neurons in L6. Secondary motor cortex (M2) inputs excited neurons mainly in L5B, including pyramidal tract neurons. In contrast, thalamocortical inputs from anterior motor-related thalamic regions, including VA/VL (ventral anterior thalamic nucleus/ventrolateral thalamic nucleus), targeted neurons in L2/3 through L5B, but avoided L6. Inputs from posterior sensory-related thalamic areas, including POm (posterior thalamic nuclear group), targeted neurons only in the upper layers (L2/3 and L5A), similar to inputs from somatosensory (barrel) cortex. Our results show that long-range excitatory inputs target vM1 pyramidal neurons in a layer-specific manner. Inputs from sensory-related cortical and thalamic areas preferentially target the upper-layer pyramidal neurons in vM1. In contrast, inputs from OC and M2, areas associated with volitional and cognitive aspects of movements, bypass local circuitry and have direct monosynaptic access to neurons projecting to brainstem and thalamus.
Assuntos
Córtex Cerebral/fisiologia , Córtex Motor/fisiologia , Neurônios/fisiologia , Tratos Piramidais/fisiologia , Tálamo/fisiologia , Animais , Córtex Cerebral/citologia , Interpretação Estatística de Dados , Vias Eferentes/citologia , Vias Eferentes/fisiologia , Estimulação Elétrica , Fenômenos Eletrofisiológicos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Motor/citologia , Técnicas de Patch-Clamp , Ponte/citologia , Ponte/fisiologia , Tratos Piramidais/citologia , Tálamo/citologiaRESUMO
GABAergic terminals of chandelier cells exclusively innervate the axon initial segment (AIS) of excitatory neurons. Although the anatomy of these synapses has been well-studied in several brain areas, relatively little is known about their physiological properties. Using vesicular γ-aminobutyric acid transporter-channelrhodopsin 2-enhanced yellow fluorescence protein (VGAT-ChR2-YFP)-expressing mice and a novel fibreoptic 'laserspritzer' approach that we developed, we investigated the physiological properties of axo-axonic synapses (AASs) in brain slices from the piriform cortex (PC) of mice. AASs were in close proximity to voltage-gated Na(+) (NaV) channels located at the AIS. AASs were selectively activated by a 5 µm laserspritzer placed in close proximity to the AIS. Under a minimal laser stimulation condition and using whole-cell somatic voltage-clamp recordings, the amplitudes and kinetics of IPSCs mediated by AASs were similar to those mediated by perisomatic inhibitions. Results were further validated with channelrhodopsin 2-assisted circuit mapping (CRACM) of the entire inhibitory inputs map. For the first time, we revealed that the laserspritzer-induced AAS-IPSCs persisted in the presence of TTX and TEA but not 4-AP. Next, using gramicidin-based perforated patch recordings, we found that the GABA reversal potential (EGABA) was -73.6 ± 1.2 mV when induced at the AIS and -72.8 ± 1.1 mV when induced at the perisomatic site. Our anatomical and physiological results lead to the novel conclusions that: (1) AASs innervate the entire length of the AIS, as opposed to forming a highly concentrated cartridge, (2) AAS inhibition suppresses action potentials and epileptiform activity more robustly than perisomatic inhibitions, and (3) AAS activation alone can be sufficient to inhibit action potential generation and epileptiform activities in vitro.
Assuntos
Axônios/fisiologia , Neurônios GABAérgicos/fisiologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Inibição Neural/fisiologia , Optogenética/métodos , Animais , Camundongos , Técnicas de Patch-Clamp , Sinapses/fisiologiaRESUMO
Learning motor skills requires plasticity in the primary motor cortex (M1), including changes in inhibitory circuitry. But how inhibitory synaptic connections change during skill acquisition and whether this varies over development is not fully understood. This study assesses the normal developmental trajectory of motor learning and then addresses inhibitory connectivity changes after motor learning. We trained mice of both sexes to run on a custom accelerating rotarod at ages from postnatal day (P) 20 to P120, tracking paw position and quantifying time to fall and changes in gait pattern. Performance improved most rapidly between P30-60, while paw position and gait patterns change with learning, though differently between age groups. To address circuit changes, we labeled task-active and task-inactive pyramidal cells with CaMPARI2, a genetically encoded activity marker. We then evoked inhibitory responses (IPSCs) from two major interneuron types: parvalbumin-expressing (PV+) interneurons and somatostatin-expressing (SOM+) interneurons. After one training day, PV-mediated inhibition is greater in task-active cells, while SOM-mediated inhibition is not different. These results suggest early changes in PV-mediated inhibition may support motor skill acquisition in mice. Whether PV-mediated inhibitory changes persist or changes in SOM+ interneuron connections arise later in training remains to be tested.
RESUMO
The cardinal symptoms of Parkinson's disease (PD) such as bradykinesia and akinesia are debilitating, and treatment options remain inadequate. The loss of nigrostriatal dopamine neurons in PD produces motor symptoms by shifting the balance of striatal output from the direct (go) to indirect (no-go) pathway in large part through changes in the excitatory connections and intrinsic excitabilities of the striatal projection neurons (SPNs). Here, we report using two different experimental models that a transient increase in striatal dopamine and enhanced D1 receptor activation, during 6-OHDA dopamine depletion, prevent the loss of mature spines and dendritic arbors on direct pathway projection neurons (dSPNs) and normal motor behavior for up to 5 months. The primary motor cortex and midline thalamic nuclei provide the major excitatory connections to SPNs. Using ChR2-assisted circuit mapping to measure inputs from motor cortex M1 to dorsolateral dSPNs, we observed a dramatic reduction in both experimental model mice and controls following dopamine depletion. Changes in the intrinsic excitabilities of SPNs were also similar to controls following dopamine depletion. Future work will examine thalamic connections to dSPNs. The findings reported here reveal previously unappreciated plasticity mechanisms within the basal ganglia that can be leveraged to treat the motor symptoms of PD.
RESUMO
To meet the high energy demands of brain function, cerebral blood flow (CBF) parallels changes in neuronal activity by a mechanism known as neurovascular coupling (NVC). However, which neurons play a role in mediating NVC is not well understood. Here, we identify in mice and humans a specific population of cortical GABAergic neurons that co-express neuronal nitric oxide synthase and tachykinin receptor 1 (Tacr1). Through whole-tissue clearing, we demonstrate that Tacr1 neurons extend local and long-range projections across functionally connected cortical areas. We show that whisker stimulation elicited Tacr1 neuron activity in the barrel cortex through feedforward excitatory pathways. Additionally, through optogenetic experiments, we demonstrate that Tacr1 neurons are instrumental in mediating CBF through the relaxation of mural cells in a similar fashion to whisker stimulation. Finally, by electron microscopy, we observe that Tacr1 processes contact astrocytic endfeet. These findings suggest that Tacr1 neurons integrate cortical activity to mediate NVC.
Assuntos
Acoplamento Neurovascular , Animais , Camundongos , Acoplamento Neurovascular/fisiologia , Humanos , Neurônios/metabolismo , Neurônios/fisiologia , Vibrissas/fisiologia , Camundongos Endogâmicos C57BL , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/fisiologia , Masculino , Córtex Cerebral/fisiologia , Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Óxido Nítrico Sintase Tipo I/metabolismoRESUMO
Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (DL-threo-ß-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.
Assuntos
Sistema X-AG de Transporte de Aminoácidos/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Transmissão Sináptica/fisiologia , Tálamo/fisiologia , Vias Visuais/fisiologia , Sistema X-AG de Transporte de Aminoácidos/antagonistas & inibidores , Animais , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Transmissão Sináptica/efeitos dos fármacos , Tálamo/efeitos dos fármacos , Vias Visuais/efeitos dos fármacosRESUMO
In mammalian cortex, feedforward excitatory connections recruit feedforward inhibition. This is often carried by parvalbumin (PV+) interneurons, which may densely connect to local pyramidal (Pyr) neurons. Whether this inhibition affects all local excitatory cells indiscriminately or is targeted to specific subnetworks is unknown. Here, we test how feedforward inhibition is recruited by using two-channel circuit mapping to excite cortical and thalamic inputs to PV+ interneurons and Pyr neurons to mouse primary vibrissal motor cortex (M1). Single Pyr and PV+ neurons receive input from both cortex and thalamus. Connected pairs of PV+ interneurons and excitatory Pyr neurons receive correlated cortical and thalamic inputs. While PV+ interneurons are more likely to form local connections to Pyr neurons, Pyr neurons are much more likely to form reciprocal connections with PV+ interneurons that inhibit them. This suggests that Pyr and PV ensembles may be organized based on their local and long-range connections, an organization that supports the idea of local subnetworks for signal transduction and processing. Excitatory inputs to M1 can thus target inhibitory networks in a specific pattern which permits recruitment of feedforward inhibition to specific subnetworks within the cortical column.
Assuntos
Córtex Motor , Parvalbuminas , Camundongos , Animais , Parvalbuminas/metabolismo , Córtex Motor/metabolismo , Células Piramidais/fisiologia , Neurônios/fisiologia , Interneurônios/fisiologia , Córtex Somatossensorial/fisiologia , Mamíferos/metabolismoRESUMO
Neocortex and striatum are topographically organized by cortical areas representing sensory and motor functions, where primary cortical areas are generally used as models for other cortical regions. But different cortical areas are specialized for distinct purposes, with sensory and motor areas lateralized for touch and motor control, respectively. Frontal areas are involved in decision making, where lateralization of function may be less important. This study contrasted the topographic precision of ipsilateral and contralateral projections from cortex based on the injection site location. While sensory cortical areas had strongly topographic outputs to ipsilateral cortex and striatum, they were weaker and not as topographically strong to contralateral targets. Motor cortex had somewhat stronger projections, but still relatively weak contralateral topography. In contrast, frontal cortical areas had high degrees of topographic similarity for both ipsilateral and contralateral projections to cortex and striatum. This contralateral connectivity reflects on the pathways in which corticostriatal computations might integrate input outside closed basal ganglia loops, enabling the two hemispheres to act as a single unit and converge on one result in motor planning and decision making.
RESUMO
Visual system circuitry, a canonical model system for the study of experience-dependent development, matures before and following the onset of vision. Sensory experience or deprivation during an early critical period results in substantial plasticity and is a crucial factor in establishing the mature circuitry. In adulthood, plasticity has been thought to be reduced or absent. However, recent studies point to the potential for change in neuronal circuits within the mature brain, raising the possibility that aberrant circuit function can be corrected. In this review, we will discuss recent exciting findings in the field of experience-dependent plasticity that advance our understanding of mechanisms underlying the activation, expression, and closure of critical periods in the visual system.
Assuntos
Modelos Neurológicos , Plasticidade Neuronal/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Humanos , Retina/crescimento & desenvolvimento , Retina/fisiologia , Transmissão Sináptica/fisiologia , Córtex Visual/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimentoRESUMO
While offering high-precision control of neural circuits, optogenetics is hampered by the necessity to implant fiber-optic waveguides in order to deliver photons to genetically engineered light-gated neurons in the brain. Unlike laser light, X-rays freely pass biological barriers. Here we show that radioluminescent Gd2(WO4)3:Eu nanoparticles, which absorb external X-rays energy and then downconvert it into optical photons with wavelengths of â¼610 nm, can be used for the transcranial stimulation of cortical neurons expressing red-shifted, â¼590-630 nm, channelrhodopsin ReaChR, thereby promoting optogenetic neural control to the practical implementation of minimally invasive wireless deep brain stimulation.
Assuntos
Nanopartículas , Optogenética , Luz , Neurônios , FótonsRESUMO
Sensory experience and spontaneous activity play important roles in development of sensory circuits; however, their relative contributions are unclear. Here, we test the role of different forms of activity on remodeling of the mouse retinogeniculate synapse. We found that the bulk of maturation occurs without patterned sensory activity over 4 days spanning eye opening. During this early developmental period, blockade of spontaneous retinal activity by tetrodotoxin, but not visual deprivation, retarded synaptic strengthening and inhibited pruning of excess retinal afferents. Later in development, synaptic remodeling becomes sensitive to changes in visually evoked activity, but only if there has been previous visual experience. Synaptic strengthening and pruning were disrupted by visual deprivation following 1 week of vision, but not by chronic deprivation from birth. Thus, spontaneous activity is necessary to drive the bulk of synaptic refinement around the time of eye opening, while sensory experience is important for the subsequent maintenance of connections.
Assuntos
Potenciais de Ação/fisiologia , Corpos Geniculados/crescimento & desenvolvimento , Plasticidade Neuronal/fisiologia , Retina/crescimento & desenvolvimento , Sinapses/fisiologia , Vias Visuais/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Diferenciação Celular/fisiologia , Escuridão/efeitos adversos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Corpos Geniculados/citologia , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Retina/citologia , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/fisiologia , Privação Sensorial/fisiologia , Bloqueadores dos Canais de Sódio/farmacologia , Sinapses/ultraestrutura , Transmissão Sináptica/fisiologia , Visão Ocular/fisiologia , Vias Visuais/citologiaRESUMO
Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity. Here, we review the visual circuitry of the mouse, describing projections from retina to thalamus, between thalamus and cortex, and within cortex. We discuss how visual circuit development leads to precise connectivity and identify synaptic loci, which can be altered by activity or experience. Plasticity extends to visual features beyond ocular dominance, involving subcortical and cortical regions, and connections between cortical inhibitory interneurons. Experience-dependent plasticity contributes to the alignment of networks spanning retina to thalamus to cortex. Disruption of this plasticity may underlie aberrant sensory processing in some neurodevelopmental disorders.
Assuntos
Dominância Ocular/fisiologia , Plasticidade Neuronal/fisiologia , Retina/fisiologia , Tálamo/fisiologia , Córtex Visual/fisiologia , Animais , Período Crítico Psicológico , Corpos Geniculados/crescimento & desenvolvimento , Corpos Geniculados/fisiologia , Núcleos Laterais do Tálamo/crescimento & desenvolvimento , Núcleos Laterais do Tálamo/fisiologia , Camundongos , Transtornos do Neurodesenvolvimento/fisiopatologia , Retina/crescimento & desenvolvimento , Colículos Superiores/crescimento & desenvolvimento , Colículos Superiores/fisiologia , Núcleo Supraquiasmático/crescimento & desenvolvimento , Núcleo Supraquiasmático/fisiologia , Sinapses/fisiologia , Tálamo/crescimento & desenvolvimento , Visão Binocular/fisiologia , Córtex Visual/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimento , Vias Visuais/fisiologiaRESUMO
In the mammalian visual system, sensory experience is widely thought to sculpt cortical circuits during a precise critical period. In contrast, subcortical regions, such as the thalamus, were thought to develop at earlier ages in a vision-independent manner. Recent studies at the retinogeniculate synapse, however, have demonstrated an influence of vision on the formation of synaptic circuits in the thalamus. In mice, dark rearing from birth does not alter normal developmental maturation of the connection between retina and thalamus. However, deprivation 20 d after birth [postnatal day 20 (p20)] resulted in dramatic weakening of synaptic strength and an increase in the number of retinal inputs that innervate a thalamic relay neuron. Here, by quantifying changes in synaptic strength and connectivity in response to different time windows of deprivation, we find that several days of vision after eye opening is necessary for triggering experience-dependent plasticity. Shorter periods of visual experience do not permit similar experience-dependent synaptic reorganization. Furthermore, changes in connectivity are rapidly reversible simply by restoring normal vision. However, similar plasticity did not occur when shifting the onset of deprivation to p25. Although synapses still weakened, recruitment of additional retinal inputs no longer occurred. Therefore, synaptic circuits in the visual thalamus are unexpectedly malleable during a late developmental period, after the time when normal synapse elimination and pruning has occurred. This thalamic sensitive period overlaps temporally with experience-dependent changes in the cortex, suggesting that subcortical plasticity may influence cortical responses to sensory experience.