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1.
J Neurosci ; 44(15)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38429106

RESUMEN

Adenosinergic modulation in the PFC is recognized for its involvement in various behavioral aspects including sleep homoeostasis, decision-making, spatial working memory and anxiety. While the principal cells of layer 6 (L6) exhibit a significant morphological diversity, the detailed cell-specific regulatory mechanisms of adenosine in L6 remain unexplored. Here, we quantitatively analyzed the morphological and electrophysiological parameters of L6 neurons in the rat medial prefrontal cortex (mPFC) using whole-cell recordings combined with morphological reconstructions. We were able to identify two different morphological categories of excitatory neurons in the mPFC of both juvenile and young adult rats with both sexes. These categories were characterized by a leading dendrite that was oriented either upright (toward the pial surface) or inverted (toward the white matter). These two excitatory neuron subtypes exhibited different electrophysiological and synaptic properties. Adenosine at a concentration of 30 µM indiscriminately suppressed connections with either an upright or an inverted presynaptic excitatory neuron. However, using lower concentrations of adenosine (10 µM) revealed that synapses originating from L6 upright neurons have a higher sensitivity to adenosine-induced inhibition of synaptic release. Adenosine receptor activation causes a reduction in the probability of presynaptic neurotransmitter release that could be abolished by specifically blocking A1 adenosine receptors (A1ARs) using 8-cyclopentyltheophylline (CPT). Our results demonstrate a differential expression level of A1ARs at presynaptic sites of two functionally and morphologically distinct subpopulations of L6 principal neurons, suggesting the intricate functional role of adenosine in neuronal signaling in the brain.


Asunto(s)
Neuronas , Células Piramidales , Femenino , Masculino , Ratas , Animales , Células Piramidales/fisiología , Neuronas/fisiología , Sinapsis/fisiología , Corteza Prefrontal/fisiología , Adenosina/farmacología , Adenosina/fisiología
2.
Cereb Cortex ; 34(9)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39344196

RESUMEN

Three major types of GABAergic interneurons, parvalbumin-, somatostatin-, and vasoactive intestinal peptide-expressing (PV, SOM, VIP) cells, play critical but distinct roles in the cortical microcircuitry. Their specific electrophysiology and connectivity shape their inhibitory functions. To study the network dynamics and signal processing specific to these cell types in the cerebral cortex, we developed a multi-layer model incorporating biologically realistic interneuron parameters from rodent somatosensory cortex. The model is fitted to in vivo data on cell-type-specific population firing rates. With a protocol of cell-type-specific stimulation, network responses when activating different neuron types are examined. The model reproduces the experimentally observed inhibitory effects of PV and SOM cells and disinhibitory effect of VIP cells on excitatory cells. We further create a version of the model incorporating cell-type-specific short-term synaptic plasticity (STP). While the ongoing activity with and without STP is similar, STP modulates the responses of Exc, SOM, and VIP cells to cell-type-specific stimulation, presumably by changing the dominant inhibitory pathways. With slight adjustments, the model also reproduces sensory responses of specific interneuron types recorded in vivo. Our model provides predictions on network dynamics involving cell-type-specific short-term plasticity and can serve to explore the computational roles of inhibitory interneurons in sensory functions.


Asunto(s)
Interneuronas , Modelos Neurológicos , Plasticidad Neuronal , Corteza Somatosensorial , Corteza Somatosensorial/fisiología , Corteza Somatosensorial/citología , Interneuronas/fisiología , Plasticidad Neuronal/fisiología , Animales , Péptido Intestinal Vasoactivo/metabolismo , Potenciales de Acción/fisiología , Parvalbúminas/metabolismo , Red Nerviosa/fisiología , Somatostatina/metabolismo , Ratas
3.
Cereb Cortex ; 32(10): 2095-2111, 2022 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-34628499

RESUMEN

Neocortical layer 6 plays a crucial role in sensorimotor co-ordination and integration through functionally segregated circuits linking intracortical and subcortical areas. We performed whole-cell recordings combined with morphological reconstructions to identify morpho-electric types of layer 6A pyramidal cells (PCs) in rat barrel cortex. Cortico-thalamic (CT), cortico-cortical (CC), and cortico-claustral (CCla) PCs were classified based on their distinct morphologies and have been shown to exhibit different electrophysiological properties. We demonstrate that these three types of layer 6A PCs innervate neighboring excitatory neurons with distinct synaptic properties: CT PCs establish weak facilitating synapses onto other L6A PCs; CC PCs form synapses of moderate efficacy, while synapses made by putative CCla PCs display the highest release probability and a marked short-term depression. For excitatory-inhibitory synaptic connections in layer 6, both the presynaptic PC type and the postsynaptic interneuron type govern the dynamic properties of the respective synaptic connections. We have identified a functional division of local layer 6A excitatory microcircuits which may be responsible for the differential temporal engagement of layer 6 feed-forward and feedback networks. Our results provide a basis for further investigations on the long-range CC, CT, and CCla pathways.


Asunto(s)
Células Piramidales , Sinapsis , Animales , Potenciales Postsinápticos Excitadores/fisiología , Interneuronas/fisiología , Vías Nerviosas/fisiología , Células Piramidales/fisiología , Ratas , Sinapsis/fisiología
4.
Cereb Cortex ; 31(1): 32-47, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-32829414

RESUMEN

GABAergic interneurons in different cortical areas play important roles in diverse higher-order cognitive functions. The heterogeneity of interneurons is well characterized in different sensory cortices, in particular in primary somatosensory and visual cortex. However, the structural and functional properties of the medial prefrontal cortex (mPFC) interneurons have received less attention. In this study, a cluster analysis based on axonal projection patterns revealed four distinct clusters of L6 interneurons in rat mPFC: Cluster 1 interneurons showed axonal projections similar to Martinotti-like cells extending to layer 1, cluster 2 displayed translaminar projections mostly to layer 5, and cluster 3 interneuron axons were confined to the layer 6, whereas those of cluster 4 interneurons extend also into the white matter. Correlations were found between neuron location and axonal distribution in all clusters. Moreover, all cluster 1 L6 interneurons showed a monotonically adapting firing pattern with an initial high-frequency burst. All cluster 2 interneurons were fast-spiking, while neurons in cluster 3 and 4 showed heterogeneous firing patterns. Our data suggest that L6 interneurons that have distinct morphological and physiological characteristics are likely to innervate different targets in mPFC and thus play differential roles in the L6 microcircuitry and in mPFC-associated functions.


Asunto(s)
Interneuronas/fisiología , Red Nerviosa/citología , Red Nerviosa/fisiología , Corteza Prefrontal/citología , Corteza Prefrontal/fisiología , Potenciales de Acción , Animales , Axones/fisiología , Membrana Celular/fisiología , Fenómenos Electrofisiológicos , Neuronas GABAérgicas/fisiología , Procesamiento de Imagen Asistido por Computador , Masculino , Técnicas de Placa-Clamp , Ratas , Ratas Wistar , Sustancia Blanca/citología
5.
Cereb Cortex ; 30(6): 3528-3542, 2020 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-32026946

RESUMEN

Acetylcholine (ACh) is known to regulate cortical activity during different behavioral states, for example, wakefulness and attention. Here we show a differential expression of muscarinic ACh receptors (mAChRs) and nicotinic ACh receptors (nAChRs) in different layer 6A (L6A) pyramidal cell (PC) types of somatosensory cortex. At low concentrations, ACh induced a persistent hyperpolarization in corticocortical (CC) but a depolarization in corticothalamic (CT) L6A PCs via M 4 and M1 mAChRs, respectively. At ~ 1 mM, ACh depolarized exclusively CT PCs via α4ß2 subunit-containing nAChRs without affecting CC PCs. Miniature EPSC frequency in CC PCs was decreased by ACh but increased in CT PCs. In synaptic connections with a presynaptic CC PC, glutamate release was suppressed via M4 mAChR activation but enhanced by nAChRs via α4ß2 nAChRs when the presynaptic neuron was a CT PC. Thus, in L6A, the interaction of mAChRs and nAChRs results in an altered excitability and synaptic release, effectively strengthening CT output while weakening CC synaptic signaling.


Asunto(s)
Acetilcolina/metabolismo , Neocórtex/metabolismo , Células Piramidales/metabolismo , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Transmisión Sináptica/fisiología , Acetilcolina/farmacología , Animales , Agonistas Colinérgicos/farmacología , Potenciales Postsinápticos Excitadores , Ácido Glutámico/metabolismo , Neocórtex/efectos de los fármacos , Vías Nerviosas , Técnicas de Placa-Clamp , Células Piramidales/efectos de los fármacos , Ratas , Receptor Muscarínico M1/efectos de los fármacos , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M4/efectos de los fármacos , Receptor Muscarínico M4/metabolismo , Receptores Muscarínicos/efectos de los fármacos , Receptores Nicotínicos/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Tálamo
6.
Cereb Cortex ; 28(4): 1439-1457, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29329401

RESUMEN

GABAergic interneurons are notorious for their heterogeneity, despite constituting a small fraction of the neuronal population in the neocortex. Classification of interneurons is crucial for understanding their widespread cortical functions as they provide a complex and dynamic network, balancing excitation and inhibition. Here, we investigated different types of non-fast-spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on a combination of morphological and electrophysiological parameters, we identified 5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting interneurons, 2) locally projecting non-Martinotti-like interneurons, 3) supra-granular projecting Martinotti-like interneurons, 4) intra-columnar projecting VIP-like interneurons, and 5) locally projecting neurogliaform-like interneurons. Trans-columnar projecting interneurons are one of the most striking interneuron types, which have not been described so far in Layer 4. They feature extensive axonal collateralization not only in their home barrel but also in adjacent barrels. Furthermore, we identified that most of the L4 nFS interneurons express somatostatin, while few are positive for the transcription factor Prox1. The morphological and electrophysiological characterization of different L4 nFS interneuron types presented here provides insights into their synaptic connectivity and functional role in cortical information processing.


Asunto(s)
Corteza Cerebral/citología , Neuronas GABAérgicas/fisiología , Potenciales de la Membrana/fisiología , Red Nerviosa/fisiología , Animales , Animales Recién Nacidos , Axones/fisiología , Dendritas/fisiología , Femenino , Imagenología Tridimensional , Técnicas In Vitro , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Modelos Neurológicos , Técnicas de Placa-Clamp , Análisis de Componente Principal , Ratas , Péptido Intestinal Vasoactivo/metabolismo
7.
Nat Rev Neurosci ; 14(3): 202-16, 2013 03.
Artículo en Inglés | MEDLINE | ID: mdl-23385869

RESUMEN

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.


Asunto(s)
Algoritmos , Corteza Cerebral/citología , Interneuronas/clasificación , Interneuronas/citología , Terminología como Asunto , Ácido gamma-Aminobutírico/metabolismo , Animales , Teorema de Bayes , Corteza Cerebral/metabolismo , Análisis por Conglomerados , Humanos , Interneuronas/metabolismo
8.
Cereb Cortex ; 27(9): 4411-4422, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27522071

RESUMEN

Adenosine is considered to be a key regulator of sleep homeostasis by promoting slow-wave sleep through inhibition of the brain's arousal centers. However, little is known about the effect of adenosine on neuronal network activity at the cellular level in the neocortex. Here, we show that adenosine differentially modulates synaptic transmission between different types of neurons in cortical layer 4 (L4) through activation of pre- and/or postsynaptically located adenosine A1 receptors. In recurrent excitatory connections between L4 spiny neurons, adenosine suppresses synaptic transmission through activation of both pre- and postsynaptic A1 receptors. In reciprocal excitatory and inhibitory connections between L4 spiny neurons and interneurons, adenosine strongly suppresses excitatory transmission via activating presynaptic A1 receptors but only slightly suppresses inhibitory transmission via activating postsynaptic A1 receptors. Adenosine has no effect on inhibitory transmission between L4 interneurons. The effect of adenosine is concentration dependent and first visible at a concentration of 1 µM. The effect of adenosine is blocked by the specific A1 receptor antagonist, 8-cyclopentyltheophylline or the nonspecific adenosine receptor antagonist, caffeine. By differentially affecting excitatory and inhibitory synaptic transmission, adenosine changes the excitation-inhibition balance and causes an overall shift to lower excitability in L4 primary somatosensory (barrel) cortical microcircuits.


Asunto(s)
Adenosina/farmacología , Corteza Somatosensorial/efectos de los fármacos , Sinapsis/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Adenosina/metabolismo , Animales , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Interneuronas/efectos de los fármacos , Células Piramidales/efectos de los fármacos , Células Piramidales/fisiología , Ratas Wistar , Receptor de Adenosina A1/efectos de los fármacos , Sueño/efectos de los fármacos , Transmisión Sináptica/fisiología
9.
Cereb Cortex ; 27(2): 1011-1026, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-26637449

RESUMEN

The fate of the subplate (SP) is still a matter of debate. The SP and layer 6 (which is ontogenetically the oldest and innermost neocortical lamina) develop coincidentally. Yet, the function of sublamina 6B is largely unknown. It has been suggested that it consists partly of neurons from the transient SP, however, experimental evidence for this hypothesis is still missing. To obtain first insights into the neuronal complement of layer 6B in the somatosensory rat barrel cortex, we used biocytin stainings of SP neurons (aged 0-4 postnatal days, PND) and layer 6B neurons (PND 11-35) obtained during in vitro whole-cell patch-clamp recordings. Neurons were reconstructed for a quantitative characterization of their axonal and dendritic morphology. An unsupervised cluster analysis revealed that the SP and layer 6B consist of heterogeneous but comparable neuronal cell populations. Both contain 5 distinct spine-bearing cell types whose relative fractions change with increasing age. Pyramidal cells were more prominent in layer 6B, whereas non-pyramidal neurons were less frequent. Because of the high morphological similarity of SP and layer 6B neurons, we suggest that layer 6B consists of persistent non-pyramidal neurons from the SP and cortical L6B pyramidal neurons.


Asunto(s)
Neocórtex/anatomía & histología , Animales , Animales Recién Nacidos , Axones/fisiología , Axones/ultraestructura , Polaridad Celular , Dendritas/fisiología , Dendritas/ultraestructura , Espinas Dendríticas/fisiología , Espinas Dendríticas/ultraestructura , Procesamiento de Imagen Asistido por Computador , Neocórtex/citología , Neocórtex/diagnóstico por imagen , Neuronas/fisiología , Técnicas de Placa-Clamp , Células Piramidales/fisiología , Células Piramidales/ultraestructura , Ratas , Ratas Wistar , Corteza Somatosensorial/anatomía & histología , Corteza Somatosensorial/citología , Corteza Somatosensorial/crecimiento & desarrollo
10.
Cereb Cortex ; 26(4): 1569-1579, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25595180

RESUMEN

Excitatory connections between neocortical layer 4 (L4) and L6 are part of the corticothalamic feedback microcircuitry. Here we studied the intracortical element of this feedback loop, the L4 spiny neuron-to-L6 pyramidal cell connection. We found that the distribution of synapses onto both putative corticothalamic (CT) and corticocortical (CC) L6 pyramidal cells (PCs) depends on the presynaptic L4 neuron type but is independent of the postsynaptic L6 PC type. L4 spiny stellate cells establish synapses on distal apical tuft dendrites of L6 PCs and elicit slow unitary excitatory postsynaptic potentials (uEPSPs) in L6 somata. In contrast, the majority of L4 star pyramidal neurons target basal and proximal apical oblique dendrites of L6 PCs and show fast uEPSPs. Compartmental modeling suggests that the slow uEPSP time course is primarily the result of dendritic filtering. This suggests that the dendritic target specificity of the 2 L4 spiny neuron types is due to their different axonal projection patterns across cortical layers. The preferential dendritic targeting by different L4 neuron types may facilitate the generation of dendritic Ca(2+) or Na(+) action potentials in L6 PCs; this could play a role in synaptic gain modulation in the corticothalamic pathway.


Asunto(s)
Axones/fisiología , Dendritas/fisiología , Células Piramidales/citología , Células Piramidales/fisiología , Corteza Somatosensorial/citología , Corteza Somatosensorial/fisiología , Sinapsis/fisiología , Animales , Potenciales Postsinápticos Excitadores , Potenciales de la Membrana , Ratas , Ratas Wistar
11.
Cereb Cortex ; 25(3): 788-805, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24108807

RESUMEN

The medial prefrontal cortex (mPFC) has been implicated in cognitive and executive processes including decision making, working memory and behavioral flexibility. Cortical processing depends on the interaction between distinct neuronal cell types in different cortical layers. To better understand cortical processing in the rat mPFC, we studied the diversity of pyramidal neurons using in vitro whole-cell patch clamp recordings and biocytin staining of neurons, followed by morphological analysis. Using unsupervised cluster analysis for the objective grouping of neurons, we identified more than 10 different pyramidal subtypes spread across the different cortical layers. Layer 2 pyramidal neurons possessed a unique morphology with wide apical dendritic field spans and a narrow basal field span. Layer 3 contained the only subtype that showed a burst of action potentials upon current injection. Layer 5 pyramidal neurons showed the largest voltage sags. Finally, pyramidal neurons in layer 6 (L6) showed a great variety in their morphology with 39% of L6 neurons possessing tall apical dendrites that extend into layer 1. Future experiments on the functional role of the mPFC should take into account the great diversity of pyramidal neurons.


Asunto(s)
Potenciales de la Membrana , Corteza Prefrontal/fisiología , Células Piramidales/citología , Células Piramidales/fisiología , Animales , Análisis por Conglomerados , Femenino , Masculino , Corteza Prefrontal/citología , Ratas , Ratas Wistar
12.
Cereb Cortex ; 25(4): 849-58, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24165834

RESUMEN

This computational study integrates anatomical and physiological data to assess the functional role of the lateral excitatory connections between layer 2/3 (L2/3) pyramidal cells (PCs) in shaping their response during early stages of intracortical processing of a whisker deflection (WD). Based on in vivo and in vitro recordings, and 3D reconstructions of connected pairs of L2/3 PCs, our model predicts that: 1) AMPAR and NMDAR conductances/synapse are 0.52 ± 0.24 and 0.40 ± 0.34 nS, respectively; 2) following WD, connection between L2/3 PCs induces a composite EPSPs of 7.6 ± 1.7 mV, well below the threshold for action potential (AP) initiation; 3) together with the excitatory feedforward L4-to-L2/3 connection, WD evoked a composite EPSP of 16.3 ± 3.5 mV and a probability of 0.01 to generate an AP. When considering the variability in L4 spiny neurons responsiveness, it increased to 17.8 ± 11.2 mV; this 3-fold increase in the SD yielded AP probability of 0.35; 4) the interaction between L4-to-L2/3 and L2/3-to-L2/3 inputs is highly nonlinear; 5) L2/3 dendritic morphology significantly affects L2/3 PCs responsiveness. We conclude that early stages of intracortical signaling of WD are dominated by a combination of feedforward L4-L2/3 and L2/3-L2/3 lateral connections.


Asunto(s)
Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Células Piramidales/citología , Células Piramidales/fisiología , Vibrisas/fisiología , Potenciales de Acción/fisiología , Animales , Simulación por Computador , Potenciales Postsinápticos Excitadores/fisiología , Imagenología Tridimensional , Modelos Neurológicos , Ratas , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/fisiología
13.
Cereb Cortex ; 25(3): 713-25, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24076498

RESUMEN

Synaptic connections between identified fast-spiking (FS), parvalbumin (PV)-positive interneurons, and excitatory spiny neurons in layer 4 (L4) of the barrel cortex were investigated using patch-clamp recordings and simultaneous biocytin fillings. Three distinct clusters of FS L4 interneurons were identified based on their axonal morphology relative to the barrel column suggesting that these neurons do not constitute a homogeneous interneuron population. One L4 FS interneuron type had an axonal domain strictly confined to a L4 barrel and was therefore named "barrel-confined inhibitory interneuron" (BIn). BIns established reliable inhibitory synaptic connections with L4 spiny neurons at a high connectivity rate of 67%, of which 69% were reciprocal. Unitary IPSPs at these connections had a mean amplitude of 0.9 ± 0.8 mV with little amplitude variation and weak short-term synaptic depression. We found on average 3.7 ± 1.3 putative inhibitory synaptic contacts that were not restricted to perisomatic areas. In conclusion, we characterized a novel type of barrel cortex interneuron in the major thalamo-recipient layer 4 forming dense synaptic networks with L4 spiny neurons. These networks constitute an efficient and powerful inhibitory feedback system, which may serve to rapidly reset the barrel microcircuitry following sensory activation.


Asunto(s)
Interneuronas/citología , Interneuronas/fisiología , Neuronas/citología , Neuronas/fisiología , Corteza Somatosensorial/citología , Corteza Somatosensorial/fisiología , Animales , Axones/ultraestructura , Potenciales Postsinápticos Excitadores , Potenciales Postsinápticos Inhibidores , Interneuronas/ultraestructura , Neuronas/ultraestructura , Ratas , Ratas Wistar , Corteza Somatosensorial/ultraestructura , Sinapsis/ultraestructura
14.
Cereb Cortex ; 25(3): 772-87, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24108800

RESUMEN

The neuromodulator adenosine is widely considered to be a key regulator of sleep homeostasis and an indicator of sleep need. Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date. To that purpose, we performed in vitro whole-cell patch-clamp recordings and biocytin staining of pyramidal neurons and interneurons throughout all layers of rat prefrontal and somatosensory cortex, followed by morphological analysis. We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location. Interneurons and pyramidal neurons in layer 2 and a subpopulation of layer 3 pyramidal neurons that displayed regular spiking were insensitive to adenosine application, whereas other pyramidal cells in layers 3-6 were hyperpolarized (range 1.2-10.8 mV). Broad tufted pyramidal neurons with little spike adaptation showed a small adenosine response, whereas slender tufted pyramidal neurons with substantial adaptation showed a bigger response. These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening.


Asunto(s)
Adenosina/fisiología , Interneuronas/fisiología , Corteza Prefrontal/fisiología , Células Piramidales/fisiología , Corteza Somatosensorial/fisiología , Adenosina/farmacología , Agonistas del Receptor de Adenosina A1 , Antagonistas del Receptor de Adenosina A1 , Animales , Femenino , Interneuronas/citología , Interneuronas/efectos de los fármacos , Masculino , Potenciales de la Membrana/efectos de los fármacos , Corteza Prefrontal/citología , Corteza Prefrontal/efectos de los fármacos , Células Piramidales/citología , Células Piramidales/efectos de los fármacos , Ratas , Ratas Wistar , Corteza Somatosensorial/citología , Corteza Somatosensorial/efectos de los fármacos
15.
Cereb Cortex ; 23(12): 2803-17, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22944531

RESUMEN

Neocortical lamina 6B (L6B) is a largely unexplored layer with a very heterogeneous cellular composition. To date, only little is known about L6B neurons on a systematic and quantitative basis. We investigated the morphological and electrophysiological properties of excitatory L6B neurons in the rat somatosensory barrel cortex using whole-cell patch-clamp recordings and simultaneous biocytin fillings. Subsequent histological processing and computer-assisted 3D reconstructions provided the basis for a classification of excitatory L6B neurons according to their structural and functional characteristics. Three distinct clusters of excitatory L6B neurons were identified: (C1) pyramidal neurons with an apical dendrite pointing towards the pial surface, (C2) neurons with a prominent, "apical"-like dendrite not oriented towards the pia, and (C3) multipolar spiny neurons without any preferential dendritic orientation. The second group could be further subdivided into three categories termed inverted, "tangentially" oriented and "horizontally" oriented neurons. Furthermore, based on the axonal domain two subcategories of L6B pyramidal cells were identified that had either a more barrel-column confined or an extended axonal field. The classification of excitatory L6B neurons provided here may serve as a basis for future studies on the structure, function, and synaptic connectivity of L6B neurons.


Asunto(s)
Neuronas/citología , Neuronas/fisiología , Corteza Somatosensorial/citología , Corteza Somatosensorial/fisiología , Animales , Axones/fisiología , Recuento de Células , Dendritas/fisiología , Femenino , Masculino , Ratas , Ratas Wistar
16.
Commun Biol ; 7(1): 885, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033173

RESUMEN

Rhythmic brain activity is critical to many brain functions and is sensitive to neuromodulation, but so far very few studies have investigated this activity on the cellular level in vitro in human brain tissue samples. This study reveals and characterizes a novel rhythmic network activity in the human neocortex. Using intracellular patch-clamp recordings of human cortical neurons, we identify large rhythmic depolarizations (LRDs) driven by glutamate release but not by GABA. These LRDs are intricate events made up of multiple depolarizing phases, occurring at ~0.3 Hz, have large amplitudes and long decay times. Unlike human tissue, rat neocortex layers 2/3 exhibit no such activity under identical conditions. LRDs are mainly observed in a subset of L2/3 interneurons that receive substantial excitatory inputs and are likely large basket cells based on their morphology. LRDs are highly sensitive to norepinephrine (NE) and acetylcholine (ACh), two neuromodulators that affect network dynamics. NE increases LRD frequency through ß-adrenergic receptor activity while ACh decreases it via M4 muscarinic receptor activation. Multi-electrode array recordings show that NE enhances and synchronizes oscillatory network activity, whereas ACh causes desynchronization. Thus, NE and ACh distinctly modulate LRDs, exerting specific control over human neocortical activity.


Asunto(s)
Acetilcolina , Neocórtex , Norepinefrina , Humanos , Acetilcolina/farmacología , Norepinefrina/farmacología , Neocórtex/fisiología , Neocórtex/metabolismo , Neocórtex/citología , Neocórtex/efectos de los fármacos , Masculino , Femenino , Animales , Persona de Mediana Edad , Ratas , Anciano , Periodicidad , Neuronas/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Interneuronas/fisiología , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Adulto
17.
Nat Rev Neurosci ; 9(7): 557-68, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18568015

RESUMEN

Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.


Asunto(s)
Corteza Cerebral/citología , Interneuronas , Ácido gamma-Aminobutírico/metabolismo , Potenciales de Acción , Axones/ultraestructura , Corteza Cerebral/metabolismo , Humanos , Interneuronas/clasificación , Interneuronas/citología , Interneuronas/metabolismo , Sinapsis/ultraestructura
18.
Front Cell Neurosci ; 17: 1257803, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37744882

RESUMEN

Cortical layer 6b is considered by many to be a remnant of the subplate that forms during early stages of neocortical development, but its role in the adult is not well understood. Its neuronal complement has only recently become the subject of systematic studies, and its axonal projections and synaptic input structures have remained largely unexplored despite decades of research into neocortical function. In recent years, however, layer 6b (L6b) has attracted increasing attention and its functional role is beginning to be elucidated. In this review, I will attempt to provide an overview of what is currently known about the excitatory and inhibitory neurons in this layer, their pre- and postsynaptic connectivity, and their functional implications. Similarities and differences between different cortical areas will be highlighted. Finally, layer 6b neurons are highly responsive to several neuropeptides such as orexin/hypocretin, neurotensin and cholecystokinin, in some cases exclusively. They are also strongly controlled by neurotransmitters such as acetylcholine and norepinephrine. The interaction of these neuromodulators with L6b microcircuitry and its functional consequences will also be discussed.

19.
Front Synaptic Neurosci ; 15: 1274383, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37731775

RESUMEN

Information transfer between principal neurons in neocortex occurs through (glutamatergic) synaptic transmission. In this focussed review, we provide a detailed overview on the strength of synaptic neurotransmission between pairs of excitatory neurons in human and laboratory animals with a specific focus on data obtained using patch clamp electrophysiology. We reach two major conclusions: (1) the synaptic strength, measured as unitary excitatory postsynaptic potential (or uEPSP), is remarkably consistent across species, cortical regions, layers and/or cell-types (median 0.5 mV, interquartile range 0.4-1.0 mV) with most variability associated with the cell-type specific connection studied (min 0.1-max 1.4 mV), (2) synaptic function cannot be generalized across human and rodent, which we exemplify by discussing the differences in anatomical and functional properties of pyramidal-to-pyramidal connections within human and rodent cortical layers 2 and 3. With only a handful of studies available on synaptic transmission in human, it is obvious that much remains unknown to date. Uncovering the shared and divergent principles of synaptic transmission across species however, will almost certainly be a pivotal step toward understanding human cognitive ability and brain function in health and disease.

20.
Proc Natl Acad Sci U S A ; 106(28): 11753-8, 2009 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-19564614

RESUMEN

Neocortical acetylcholine (ACH) release is known to enhance signal processing by increasing the amplitude and signal-to-noise ratio (SNR) of sensory responses. It is widely accepted that the larger sensory responses are caused by a persistent increase in the excitability of all cortical excitatory neurons. Here, contrary to this concept, we show that ACH persistently inhibits layer 4 (L4) spiny neurons, the main targets of thalamocortical inputs. Using whole-cell recordings in slices of rat primary somatosensory cortex, we demonstrate that this inhibition is specific to L4 and contrasts with the ACH-induced persistent excitation of pyramidal cells in L2/3 and L5. We find that this inhibition is induced by postsynaptic M(4)-muscarinic ACH receptors and is mediated by the opening of inwardly rectifying potassium (K(ir)) channels. Pair recordings of L4 spiny neurons show that ACH reduces synaptic release in the L4 recurrent microcircuit. We conclude that ACH has a differential layer-specific effect that results in a filtering of weak sensory inputs in the L4 recurrent excitatory microcircuit and a subsequent amplification of relevant inputs in L2/3 and L5 excitatory microcircuits. This layer-specific effect may contribute to improve cortical SNR.


Asunto(s)
Acetilcolina/metabolismo , Neuronas/metabolismo , Corteza Somatosensorial/metabolismo , Transmisión Sináptica/fisiología , Acetilcolina/farmacología , Vías Aferentes/fisiología , Animales , Neuronas/efectos de los fármacos , Canales de Potasio de Rectificación Interna/metabolismo , Ratas , Ratas Wistar , Receptores Muscarínicos/metabolismo , Transmisión Sináptica/efectos de los fármacos
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