Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
J Neurosci ; 44(20)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38604778

RESUMEN

The reversal potential refers to the membrane potential at which the net current flow through a channel reverses direction. The reversal potential is determined by transmembrane ion gradients and, in turn, determines how the channel's activity will affect the membrane potential. Traditional investigation into the reversal potential of inhibitory ligand-gated ion channels (EInh) has relied upon the activation of endogenous receptors, such as the GABA-A receptor (GABAAR). There are, however, challenges associated with activating endogenous receptors, including agonist delivery, isolating channel responses, and the effects of receptor saturation and desensitization. Here, we demonstrate the utility of using a light-gated anion channel, stGtACR2, to probe EInh in the rodent brain. Using mice of both sexes, we demonstrate that the properties of this optically activated channel make it a suitable proxy for studying GABAAR receptor-mediated inhibition. We validate this agonist-independent optogenetic strategy in vitro and in vivo and further show how it can accurately capture differences in EInh dynamics following manipulations of endogenous ion fluxes. This allows us to explore distinct resting EInh differences across genetically defined neuronal subpopulations. Using this approach to challenge ion homeostasis mechanisms in neurons, we uncover cell-specific EInh dynamics that are supported by the differential expression of endogenous ion handling mechanisms. Our findings therefore establish an effective optical strategy for revealing novel aspects of inhibitory reversal potentials and thereby expand the repertoire of optogenetics.


Asunto(s)
Potenciales de la Membrana , Optogenética , Animales , Optogenética/métodos , Ratones , Masculino , Femenino , Potenciales de la Membrana/fisiología , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética , Neuronas/fisiología , Neuronas/metabolismo , Ratones Endogámicos C57BL , Inhibición Neural/fisiología , Canales Iónicos Activados por Ligandos/metabolismo , Canales Iónicos Activados por Ligandos/genética , Ratones Transgénicos
2.
Curr Biol ; 34(8): 1718-1730.e3, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38582078

RESUMEN

Recent evidence suggests that primary sensory cortical regions play a role in the integration of information from multiple sensory modalities. How primary cortical neurons integrate different sources of sensory information is unclear, partly because non-primary sensory input to a cortical sensory region is often weak or modulatory. To address this question, we take advantage of the robust representation of thermal (cooling) and tactile stimuli in mouse forelimb primary somatosensory cortex (fS1). Using a thermotactile detection task, we show that the perception of threshold-level cool or tactile information is enhanced when they are presented simultaneously, compared with presentation alone. To investigate the cortical cellular correlates of thermotactile integration, we performed in vivo extracellular recordings from fS1 in awake resting and anesthetized mice during unimodal and bimodal stimulation of the forepaw. Unimodal stimulation evoked thermal- or tactile- specific excitatory and inhibitory responses of fS1 neurons. The most prominent features of combined thermotactile stimulation are the recruitment of unimodally silent fS1 neurons, non-linear integration features, and response dynamics that favor longer response durations with additional spikes. Together, we identify quantitative and qualitative changes in cortical encoding that may underlie the improvement in perception of thermotactile surfaces during haptic exploration.


Asunto(s)
Corteza Somatosensorial , Animales , Ratones , Corteza Somatosensorial/fisiología , Tacto/fisiología , Neuronas/fisiología , Ratones Endogámicos C57BL , Miembro Anterior/fisiología , Percepción del Tacto/fisiología , Masculino , Estimulación Física
3.
bioRxiv ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38405930

RESUMEN

Although distinct thalamic nuclei encode sensory information for almost all sensory modalities, the existence of a thalamic representation of temperature with a role in thermal perception remains unclear. To address this, we performed high-density electrophysiological recordings across the entire forelimb somatosensory thalamus in awake mice, and identified an anterior and a posterior representation of temperature that spans three thalamic nuclei. We found that these parallel representations show fundamental differences in the cellular encoding of temperature which reflects their cortical output targets. While the anterior representation encodes cool only and the posterior both cool and warm; in both representations cool was more densely represented and showed shorter latency, more transient responses as compared to warm. Moreover, thalamic inactivation showed a major role in thermal perception. Our comprehensive dataset identifies the thalamus as a key structure in thermal processing and highlights a novel posterior pathway in the thalamic representation of warm and cool.

4.
Nat Commun ; 15(1): 898, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38320986

RESUMEN

Previous work identified nociceptive Schwann cells that can initiate pain. Consistent with the existence of inherently mechanosensitive sensory Schwann cells, we found that in mice, the mechanosensory function of almost all nociceptors, including those signaling fast pain, were dependent on sensory Schwann cells. In polymodal nociceptors, sensory Schwann cells signal mechanical, but not cold or heat pain. Terminal Schwann cells also surround mechanoreceptor nerve-endings within the Meissner's corpuscle and in hair follicle lanceolate endings that both signal vibrotactile touch. Within Meissner´s corpuscles, two molecularly and functionally distinct sensory Schwann cells positive for Sox10 and Sox2 differentially modulate rapidly adapting mechanoreceptor function. Using optogenetics we show that Meissner's corpuscle Schwann cells are necessary for the perception of low threshold vibrotactile stimuli. These results show that sensory Schwann cells within diverse glio-neural mechanosensory end-organs are sensors for mechanical pain as well as necessary for touch perception.


Asunto(s)
Percepción del Tacto , Tacto , Ratones , Animales , Tacto/fisiología , Nocicepción , Percepción del Tacto/fisiología , Mecanorreceptores/fisiología , Células de Schwann , Dolor , Umbral Sensorial
5.
Sci Rep ; 14(1): 1660, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238544

RESUMEN

The patch-clamp technique has revolutionized neurophysiology by allowing to study single neuronal excitability, synaptic connectivity, morphology, and the transcriptomic profile. However, the throughput in recordings is limited because of the manual replacement of patch-pipettes after each attempt which are often also unsuccessful. This has been overcome by automated cleaning the tips in detergent solutions, allowing to reuse the pipette for further recordings. Here, we developed a novel method of automated cleaning by sonicating the tips within the bath solution wherein the cells are placed, reducing the risk of contaminating the bath solution or internal solution of the recording pipette by any detergent and avoiding the necessity of a separate chamber for cleaning. We showed that the patch-pipettes can be used consecutively at least ten times and that the cleaning process does not negatively impact neither the brain slices nor other patched neurons. This method, combined with automated patch-clamp, highly improves the throughput for single and especially multiple recordings.


Asunto(s)
Detergentes , Ultrasonido , Neuronas/fisiología , Neurofisiología , Técnicas de Placa-Clamp
6.
Cereb Cortex ; 33(8): 4870-4885, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36255325

RESUMEN

In the thermal system, skin cooling is represented in the primary somatosensory cortex (S1) and the posterior insular cortex (pIC). Whether S1 and pIC are nodes in anatomically separate or overlapping thermal sensorimotor pathways is unclear, as the brain-wide connectivity of the thermal system has not been mapped. We address this using functionally targeted, dual injections of anterograde viruses or retrograde tracers into the forelimb representation of S1 (fS1) and pIC (fpIC). Our data show that inputs to fS1 and fpIC originate from separate neuronal populations, supporting the existence of parallel input pathways. Outputs from fS1 and fpIC are more widespread than their inputs, sharing a number of cortical and subcortical targets. While, axonal projections were separable, they were more overlapping than the clusters of input cells. In both fS1 and fpIC circuits, there was a high degree of reciprocal connectivity with thalamic and cortical regions, but unidirectional output to the midbrain and hindbrain. Notably, fpIC showed connectivity with regions associated with thermal processing. Together, these data indicate that cutaneous thermal information is routed to the cortex via parallel circuits and is forwarded to overlapping downstream regions for the binding of somatosensory percepts and integration with ongoing behavior.


Asunto(s)
Neuronas , Tálamo , Ratones , Animales , Vías Nerviosas/fisiología , Tálamo/fisiología , Mapeo Encefálico , Encéfalo , Corteza Somatosensorial/fisiología
7.
Nat Commun ; 12(1): 6307, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34728601

RESUMEN

It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mice. These neuronal groups, IRtPhox2b and Peri5Atoh1, are marked by expression of the pan-autonomic homeobox gene Phox2b and are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve. They are premotor to all jaw-opening and tongue muscles. Stimulation of either, in awake animals, opens the jaw, while IRtPhox2b alone also protracts the tongue. Moreover, stationary stimulation of IRtPhox2b entrains a rhythmic alternation of tongue protraction and retraction, synchronized with jaw opening and closing, that mimics lapping. Finally, fiber photometric recordings show that IRtPhox2b is active during volitional lapping. Our study identifies one of the subcortical nuclei underpinning a stereotyped feeding behavior.


Asunto(s)
Tronco Encefálico/metabolismo , Conducta Alimentaria/fisiología , Proteínas de Homeodominio/metabolismo , Maxilares/fisiología , Bulbo Raquídeo/metabolismo , Neuronas Motoras/metabolismo , Lengua/fisiología , Factores de Transcripción/metabolismo , Potenciales de Acción , Animales , Femenino , Proteínas de Homeodominio/genética , Masculino , Ratones , Ratones Noqueados , Formación Reticular/metabolismo , Factores de Transcripción/genética
8.
Nat Neurosci ; 24(1): 74-81, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33288907

RESUMEN

Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive, vibration-sensing neurons are associated with Meissner's corpuscles in the skin. In the present study, we found that USH2A, a transmembrane protein with a very large extracellular domain, was found in terminal Schwann cells within Meissner's corpuscles. Pathogenic USH2A mutations cause Usher's syndrome, associated with hearing loss and visual impairment. We show that patients with biallelic pathogenic USH2A mutations also have clear and specific impairments in vibrotactile touch perception, as do mutant mice lacking USH2A. Forepaw rapidly adapting mechanoreceptors innervating Meissner's corpuscles, recorded from Ush2a-/- mice, showed large reductions in vibration sensitivity. However, the USH2A protein was not found in sensory neurons. Thus, loss of USH2A in corpuscular end-organs reduced mechanoreceptor sensitivity as well as vibration perception. Thus, a tether-like protein is required to facilitate detection of small-amplitude vibrations essential for the perception of fine-grained tactile surfaces.


Asunto(s)
Proteínas de la Matriz Extracelular/genética , Mecanorreceptores/metabolismo , Sensación/fisiología , Vibración , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos CBA , Ratones Noqueados , Mutación/genética , Células de Schwann/fisiología , Piel/inervación , Tacto/fisiología , Síndromes de Usher/genética
9.
Neuron ; 106(5): 830-841.e3, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32208171

RESUMEN

Humans detect skin temperature changes that are perceived as warm or cool. Like humans, mice report forepaw skin warming with perceptual thresholds of less than 1°C and do not confuse warm with cool. We identify two populations of polymodal C-fibers that signal warm. Warm excites one population, whereas it suppresses the ongoing cool-driven firing of the other. In the absence of the thermosensitive TRPM2 or TRPV1 ion channels, warm perception was blunted, but not abolished. In addition, trpv1:trpa1:trpm3-/- triple-mutant mice that cannot sense noxious heat detected skin warming, albeit with reduced sensitivity. In contrast, loss or local pharmacological silencing of the cool-driven TRPM8 channel abolished the ability to detect warm. Our data are not reconcilable with a labeled line model for warm perception, with receptors firing only in response to warm stimuli, but instead support a conserved dual sensory model to unambiguously detect skin warming in vertebrates.


Asunto(s)
Fibras Nerviosas Amielínicas/fisiología , Nocicepción/fisiología , Percepción/fisiología , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPV/genética , Sensación Térmica/genética , Animales , Ratones , Ratones Noqueados , Mutación , Umbral Sensorial , Sensación Térmica/fisiología , Extremidad Superior
10.
Artículo en Inglés | MEDLINE | ID: mdl-31156420

RESUMEN

Although we know a great deal about monosynaptic connectivity, transmission and integration in the mammalian nervous system from in vitro studies, very little is known in vivo. This is partly because it is technically difficult to evoke action potentials and simultaneously record small amplitude subthreshold responses in closely (<150 µm) located pairs of neurons. To address this, we have developed in vivo two-photon targeted multiple (2-4) whole-cell patch clamp recordings of nearby neurons in superficial cortical layers 1-3. Here, we describe a step-by-step guide to this approach in the anesthetized mouse primary somatosensory cortex, including: the design of the setup, surgery, preparation of pipettes, targeting and acquisition of multiple whole-cell recordings, as well as in vivo and post hoc histology. The procedure takes ~4 h from start of surgery to end of recording and allows examinations both into the electrophysiological features of unitary excitatory and inhibitory monosynaptic inputs during different brain states as well as the synaptic mechanisms of correlated neuronal activity.

11.
Cell Rep ; 24(13): 3455-3465.e5, 2018 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-30257207

RESUMEN

Excitatory synaptic input reaches the soma of a cortical excitatory pyramidal neuron via anatomically segregated apical and basal dendrites. In vivo, dendritic inputs are integrated during depolarized network activity, but how network activity affects apical and basal inputs is not understood. Using subcellular two-photon stimulation of Channelrhodopsin2-expressing layer 2/3 pyramidal neurons in somatosensory cortex, nucleus-specific thalamic optogenetic stimulation, and paired recordings, we show that slow, depolarized network activity amplifies small-amplitude synaptic inputs targeted to basal dendrites but reduces the amplitude of all inputs from apical dendrites and the cell soma. Intracellular pharmacology and mathematical modeling suggests that the amplification of weak basal inputs is mediated by postsynaptic voltage-gated channels. Thus, network activity dynamically reconfigures the relative somatic contribution of apical and basal inputs and could act to enhance the detectability of weak synaptic inputs.


Asunto(s)
Dendritas/fisiología , Potenciales Postsinápticos Excitadores , Células Piramidales/fisiología , Corteza Somatosensorial/fisiología , Potenciales de Acción , Animales , Células Cultivadas , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Neurológicos , Corteza Somatosensorial/citología , Tálamo/citología , Tálamo/fisiología
12.
Nat Commun ; 9(1): 1540, 2018 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-29670095

RESUMEN

A defining feature of cortical layer 2/3 excitatory neurons is their sparse activity, often firing in singlets of action potentials. Local inhibitory neurons are thought to play a major role in regulating sparseness, but which cell types are recruited by single excitatory synaptic inputs is unknown. Using multiple, targeted, in vivo whole-cell recordings, we show that single uEPSPs have little effect on the firing rates of excitatory neurons and somatostatin-expressing GABA-ergic inhibitory neurons but evoke precisely timed action potentials in parvalbumin-expressing inhibitory neurons. Despite a uEPSP decay time of 7.8 ms, the evoked action potentials were almost completely restricted to the uEPSP rising phase (~0.5 ms). Evoked parvalbumin-expressing neuron action potentials go on to inhibit the local excitatory network, thus providing a pathway for single spike evoked disynaptic inhibition which may enforce sparse and precisely timed cortical signaling.


Asunto(s)
Potenciales de Acción/fisiología , Corteza Cerebral/metabolismo , Neuronas GABAérgicas/fisiología , Parvalbúminas/química , Sinapsis/fisiología , Animales , Ratones , Ratones Endogámicos C57BL , Inhibición Neural/fisiología , Técnicas de Placa-Clamp , Fotones , Programas Informáticos , Somatostatina/química , Ácido gamma-Aminobutírico/farmacología
13.
Neuron ; 97(3): 611-625.e5, 2018 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-29420933

RESUMEN

Sleep, waking, locomotion, and attention are associated with cell-type-specific changes in neocortical activity. The effect of brain state on circuit output requires understanding of how neuromodulators influence specific neuronal classes and their synapses, with normal patterns of neuromodulator release from endogenous sources. We investigated the state-dependent modulation of a ubiquitous feedforward inhibitory motif in mouse sensory cortex, local pyramidal (Pyr) inputs onto somatostatin (SST)-expressing interneurons. Paired whole-cell recordings in acute brain slices and in vivo showed that Pyr-to-SST synapses are remarkably weak, with failure rates approaching 80%. Pharmacological screening revealed that cholinergic agonists uniquely enhance synaptic efficacy. Brief, optogenetically gated acetylcholine release dramatically enhanced Pyr-to-SST input, via nicotinic receptors and presynaptic PKA signaling. Importantly, endogenous acetylcholine release preferentially activated nicotinic, not muscarinic, receptors, thus differentiating drug effects from endogenous neurotransmission. Brain state- and synapse-specific unmasking of synapses may be a powerful way to functionally rewire cortical circuits dependent on behavioral demands.


Asunto(s)
Acetilcolina/fisiología , Potenciales Postsinápticos Excitadores , Interneuronas/fisiología , Neocórtex/fisiología , Inhibición Neural , Células Piramidales/fisiología , Receptores Nicotínicos/fisiología , Animales , Prosencéfalo Basal/fisiología , Carbacol/administración & dosificación , Agonistas Colinérgicos/administración & dosificación , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Femenino , Interneuronas/metabolismo , Masculino , Ratones Endogámicos C57BL , Transducción de Señal , Somatostatina/metabolismo
14.
Front Syst Neurosci ; 12: 64, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30670952

RESUMEN

Cortical neurons process information on a background of spontaneous, ongoing activity with distinct spatiotemporal profiles defining different cortical states. During wakefulness, cortical states alter constantly in relation to behavioral context, attentional level or general motor activity. In this review article, we will discuss our current understanding of cortical states in awake rodents, how they are controlled, their impact on sensory processing, and highlight areas for future research. A common observation in awake rodents is the rapid change in spontaneous cortical activity from high-amplitude, low-frequency (LF) fluctuations, when animals are quiet, to faster and smaller fluctuations when animals are active. This transition is typically thought of as a change in global brain state but recent work has shown variation in cortical states across regions, indicating the presence of a fine spatial scale control system. In sensory areas, the cortical state change is mediated by at least two convergent inputs, one from the thalamus and the other from cholinergic inputs in the basal forebrain. Cortical states have a major impact on the balance of activity between specific subtypes of neurons, on the synchronization between nearby neurons, as well as the functional coupling between distant cortical areas. This reorganization of the activity of cortical networks strongly affects sensory processing. Thus cortical states provide a dynamic control system for the moment-by-moment regulation of cortical processing.

15.
Cell Rep ; 20(2): 308-318, 2017 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-28700934

RESUMEN

The control of targeted reaching is thought to be shaped by distinct subtypes of local GABAergic inhibitory neurons in primary forelimb motor cortex (M1). However, little is known about their action potential firing dynamics during reaching. To address this, we recorded the activity of parvalbumin-expressing (PV+) GABAergic neurons identified from a larger population of fast-spiking units and putative excitatory regular-spiking units in layer 5 of the mouse forelimb M1 during an M1-dependent, sensory-triggered reaching task. PV+ neurons showed short latency responses to the acoustic cue and vibrotactile trigger stimulus and an increase in firing at reaching onset that scaled with the amplitude of reaching. Unexpectedly, PV+ neurons fired before regular-spiking units at reach onset and showed high overall firing rates during both sensory-triggered and spontaneous reaches. Our data suggest that increasing M1 PV+ neuron firing rates may play a role in the initiation of voluntary reaching.


Asunto(s)
Neuronas GABAérgicas/metabolismo , Corteza Motora/metabolismo , Parvalbúminas/metabolismo , Potenciales de Acción/fisiología , Animales , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL
16.
Nat Neurosci ; 20(8): 1096-1103, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28628102

RESUMEN

Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.


Asunto(s)
Núcleo Arqueado del Hipotálamo/metabolismo , Peso Corporal/fisiología , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular/genética , Homeostasis/genética , Inmunoglobulinas/genética , Obesidad/metabolismo , Animales , Molécula 1 de Adhesión Celular , Metabolismo Energético/fisiología , Estudio de Asociación del Genoma Completo , Homeostasis/fisiología , Proteínas de la Membrana/metabolismo , Ratones Transgénicos , Neuronas/metabolismo , Obesidad/genética , Proopiomelanocortina/metabolismo
17.
Nat Neurosci ; 20(2): 209-218, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27941788

RESUMEN

The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors in vivo. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.


Asunto(s)
Hipersensibilidad/metabolismo , Canales Iónicos/metabolismo , Mecanorreceptores/metabolismo , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Células Receptoras Sensoriales/metabolismo , Animales , Ganglios Espinales/metabolismo , Hipersensibilidad/tratamiento farmacológico , Mecanotransducción Celular/efectos de los fármacos , Mecanotransducción Celular/fisiología , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas del Tejido Nervioso/metabolismo , Células Receptoras Sensoriales/efectos de los fármacos , Piel/inervación , Tacto/fisiología
18.
Cell Rep ; 15(11): 2387-99, 2016 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-27264185

RESUMEN

The synchronized activity of six layers of cortical neurons is critical for sensory perception and the control of voluntary behavior, but little is known about the synaptic mechanisms of cortical synchrony across layers in behaving animals. We made single and dual whole-cell recordings from the primary somatosensory forepaw cortex in awake mice and show that L2/3 and L5 excitatory neurons have layer-specific intrinsic properties and membrane potential dynamics that shape laminar-specific firing rates and subthreshold synchrony. First, while sensory and movement-evoked synaptic input was tightly correlated across layers, spontaneous action potentials and slow spontaneous subthreshold fluctuations had laminar-specific timing; second, longer duration forepaw movement was associated with a decorrelation of subthreshold activity; third, spontaneous and sensory-evoked forepaw movements were signaled more strongly by L5 than L2/3 neurons. Together, our data suggest that the degree of translaminar synchrony is dependent upon the origin (sensory, spontaneous, and movement) of the synaptic input.


Asunto(s)
Conducta Animal/fisiología , Potenciales de la Membrana/fisiología , Corteza Somatosensorial/fisiología , Animales , Extremidades/fisiología , Ratones , Movimiento/fisiología , Estimulación Física , Células Piramidales/fisiología , Corteza Somatosensorial/citología , Sinapsis/fisiología , Tacto , Vigilia
19.
Cell Rep ; 13(10): 2098-106, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26670044

RESUMEN

Little is known about the properties of monosynaptic connections between identified neurons in vivo. We made multiple (two to four) two-photon targeted whole-cell recordings from neighboring layer 2 mouse somatosensory barrel cortex pyramidal neurons in vivo to investigate excitatory monosynaptic transmission in the hyperpolarized downstate. We report that pyramidal neurons form a sparsely connected (6.7% connectivity) network with an overrepresentation of bidirectional connections. The majority of unitary excitatory postsynaptic potentials were small in amplitude (<0.5 mV), with a small minority >1 mV. The coefficient of variation (CV = 0.74) could largely be explained by the presence of synaptic failures (22%). Both the CV and failure rates were reduced with increasing amplitude. The mean paired-pulse ratio was 1.15 and positively correlated with the CV. Our approach will help bridge the gap between connectivity and function and allow investigations into the impact of brain state on monosynaptic transmission and integration.


Asunto(s)
Potenciales Postsinápticos Excitadores/fisiología , Células Piramidales/fisiología , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Técnicas de Placa-Clamp , Corteza Somatosensorial/fisiología
20.
J Neurosci ; 35(40): 13608-18, 2015 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-26446215

RESUMEN

Cortical and hippocampal oscillations play a crucial role in the encoding, consolidation, and retrieval of memory. Sharp-wave associated ripples have been shown to be necessary for the consolidation of memory. During consolidation, information is transferred from the hippocampus to the neocortex. One of the structures at the interface between hippocampus and neocortex is the subiculum. It is therefore well suited to mediate the transfer and distribution of information from the hippocampus to other areas. By juxtacellular and whole-cell-recordings in awake mice, we show here that in the subiculum a subset of pyramidal cells is activated, whereas another subset is inhibited during ripples. We demonstrate that these functionally different subgroups are predetermined by their cell subtype. Bursting cells are selectively used to transmit information during ripples, whereas the firing probability in regular firing cells is reduced. With multiple patch-clamp recordings in vitro, we show that the cell subtype-specific differences extend into the local network topology. This is reflected in an asymmetric wiring scheme where bursting cells and regular firing cells are recurrently connected among themselves but connections between subtypes exclusively exist from regular to bursting cells. Furthermore, inhibitory connections are more numerous onto regular firing cells than onto bursting cells. We conclude that the network topology contributes to the observed functional diversity of subicular pyramidal cells during sharp-wave associated ripples. SIGNIFICANCE STATEMENT: Memory consolidation is dependent on hippocampal activity patterns, so called hippocampal ripples. During these fast oscillations, memory traces are transferred from the hippocampus to the neocortex via the subiculum. We investigated the role of single cells in the subiculum during ripples and found that, dependent on their subtype, they are preferentially activated or inhibited. In addition, these two subtypes, the bursting and regular firing type, are differentially integrated into the local network: inhibitory cells are more densely connected to regular firing cells, and communication between regular and bursting cells is unidirectional. Together with earlier findings on different preferential target regions of these subtypes, we conclude that memory traces are guided to target regions of the activated cell type.


Asunto(s)
Potenciales de Acción/fisiología , Hipocampo/citología , Hipocampo/fisiología , Células Piramidales/fisiología , Factores de Edad , Animales , Estimulación Eléctrica , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Red Nerviosa/fisiología , Técnicas de Placa-Clamp , Estadísticas no Paramétricas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA