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1.
Front Hum Neurosci ; 15: 618626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613212

RESUMO

Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces (BCIs) should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. The animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions.

2.
PLoS Biol ; 18(3): e3000643, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176686

RESUMO

Communication with the hematopoietic system is a vital component of regulating brain function in health and disease. Traditionally, the major routes considered for this neuroimmune communication are by individual molecules such as cytokines carried by blood, by neural transmission, or, in more severe pathologies, by the entry of peripheral immune cells into the brain. In addition, functional mRNA from peripheral blood can be directly transferred to neurons via extracellular vesicles (EVs), but the parameters that determine their uptake are unknown. Using varied animal models that stimulate neuronal activity by peripheral inflammation, optogenetics, and selective proteasome inhibition of dopaminergic (DA) neurons, we show that the transfer of EVs from blood is triggered by neuronal activity in vivo. Importantly, this transfer occurs not only in pathological stimulation but also by neuronal activation caused by the physiological stimulus of novel object placement. This discovery suggests a continuous role of EVs under pathological conditions as well as during routine cognitive tasks in the healthy brain.


Assuntos
Células Sanguíneas/citologia , Encéfalo/metabolismo , Vesículas Extracelulares/metabolismo , Inflamação/metabolismo , Animais , Células Sanguíneas/metabolismo , Encéfalo/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Feminino , Hipocampo/fisiologia , Inflamação/induzido quimicamente , Ácido Caínico/farmacologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Transgênicos , Optogenética , Complexo de Endopeptidases do Proteassoma/metabolismo , Transdução de Sinais , Técnicas Estereotáxicas , Ubiquitina/metabolismo
3.
Cereb Cortex ; 27(12): 5784-5803, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040472

RESUMO

Parvalbumin (PV) positive interneurons exert strong effects on the neocortical excitatory network, but it remains unclear how they impact the spatiotemporal dynamics of sensory processing in the somatosensory cortex. Here, we characterized the effects of optogenetic inhibition and activation of PV interneurons on spontaneous and sensory-evoked activity in mouse barrel cortex in vivo. Inhibiting PV interneurons led to a broad-spectrum power increase both in spontaneous and sensory-evoked activity. Whisker-evoked responses were significantly increased within 20 ms after stimulus onset during inhibition of PV interneurons, demonstrating high temporal precision of PV-shaped inhibition. Multiunit activity was strongly enhanced in neighboring cortical columns, but not at the site of transduction, supporting a central and highly specific role of PV interneurons in lateral inhibition. Inversely, activating PV interneurons drastically decreased spontaneous and whisker-evoked activity in the principal column and exerted strong lateral inhibition. Histological assessment of transduced cells combined with quantitative modeling of light distribution and spike sorting revealed that only a minor fraction (~10%) of the local PV population comprising no more than a few hundred neurons is optogenetically modulated, mediating the observed prominent and widespread effects on neocortical processing.


Assuntos
Potenciais Somatossensoriais Evocados/fisiologia , Interneurônios/fisiologia , Parvalbuminas/metabolismo , Córtex Somatossensorial/fisiologia , Percepção do Tato/fisiologia , Potenciais de Ação , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microeletrodos , Optogenética , Estimulação Física , Fatores de Tempo , Vibrissas/fisiologia
4.
Elife ; 62017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28914607

RESUMO

Spontaneous slow oscillation-associated slow wave activity represents an internally generated state which is characterized by alternations of network quiescence and stereotypical episodes of neuronal activity - slow wave events. However, it remains unclear which macroscopic signal is related to these active periods of the slow wave rhythm. We used optic fiber-based calcium recordings of local neural populations in cortex and thalamus to detect neurophysiologically defined slow calcium waves in isoflurane anesthetized rats. The individual slow wave events were used for an event-related analysis of simultaneously acquired whole-brain BOLD fMRI. We identified BOLD responses directly related to onsets of slow calcium waves, revealing a cortex-wide BOLD correlate: the entire cortex was engaged in this specific type of slow wave activity. These findings demonstrate a direct relation of defined neurophysiological events to a specific BOLD activity pattern and were confirmed for ongoing slow wave activity by independent component and seed-based analyses.


Assuntos
Sinalização do Cálcio , Córtex Cerebral/fisiologia , Tálamo/fisiologia , Animais , Imageamento por Ressonância Magnética , Ratos
5.
Neuron ; 92(1): 126-142, 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27641493

RESUMO

Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in PRG-2 full knockout (KO) and in thalamus-specific KO mice prematurely entered the cortical plate, eventually innervating non-corresponding barrels. This misrouting relied on lost axonal sensitivity toward lysophosphatidic acid (LPA), which failed to repel PRG-2-deficient thalamocortical fibers. PRG-2 electroporation in the PRG-2-/- thalamus restored the aberrant cortical innervation. We identified radixin as a PRG-2 interaction partner and showed that radixin accumulation in growth cones and its LPA-dependent phosphorylation depend on its binding to specific regions within the C-terminal region of PRG-2. In vivo recordings and whisker-specific behavioral tests demonstrated sensory discrimination deficits in PRG-2-/- animals. Our data show that bioactive phospholipids and PRG-2 are critical for guiding thalamic axons to their proper cortical targets.


Assuntos
Orientação de Axônios/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Proteínas do Citoesqueleto/fisiologia , Lisofosfolipídeos/fisiologia , Proteínas de Membrana/fisiologia , Transdução de Sinais/fisiologia , Tálamo/crescimento & desenvolvimento , Animais , Córtex Cerebral/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Discriminação Psicológica/fisiologia , Cones de Crescimento/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Vias Neurais/metabolismo , Vias Neurais/fisiologia , Fosforilação , Tálamo/metabolismo
6.
J Cereb Blood Flow Metab ; 36(11): 1885-1900, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26661247

RESUMO

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping.


Assuntos
Cálcio/metabolismo , Imageamento por Ressonância Magnética/métodos , Neurônios/metabolismo , Optogenética/métodos , Córtex Somatossensorial/diagnóstico por imagem , Compostos de Anilina/química , Animais , Channelrhodopsins , Potenciais Evocados/fisiologia , Feminino , Fluoresceínas/química , Vetores Genéticos , Microscopia de Fluorescência , Fibras Ópticas , Oxigênio/sangue , Estimulação Luminosa , Ratos Endogâmicos F344 , Córtex Somatossensorial/metabolismo , Transdução Genética
7.
Methods Mol Biol ; 1148: 129-47, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24718799

RESUMO

Optogenetics allows for the specific manipulation of the activity of genetically defined cell populations in the CNS. Yet, it requires effective gene delivery, light stimulation, and readout strategies. Here, we provide a roadmap aimed at guiding the experimenter in the process of establishing an optogenetic approach tailored to a given research hypothesis in the field of neuroscience.


Assuntos
Optogenética , Animais , Comportamento Animal , Encéfalo/metabolismo , Vetores Genéticos , Humanos , Ativação do Canal Iônico/efeitos da radiação , Luz , Neurociências , Processos Fotoquímicos , Rodopsina/biossíntese , Rodopsina/genética , Ativação Transcricional/efeitos da radiação , Transdução Genética
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