scholarly journals Cell-type specific innervation of cortical pyramidal cells at their apical tufts

2019 ◽  
Author(s):  
Ali Karimi ◽  
Jan Odenthal ◽  
Florian Drawitsch ◽  
Kevin M. Boergens ◽  
Moritz Helmstaedter
Keyword(s):  
Electron Microscopy ◽  
Pyramidal Cells ◽  
Inhibitory Input ◽  
Cell Type ◽  
Layer 2 ◽  
Cell Type Specific ◽  
Cortical Regions ◽  
3D Em ◽  
Apical Dendrites ◽  
Computational Properties

ABSTRACTWe investigated the synaptic innervation of apical tufts of cortical pyramidal cells in a region between layers 1 and 2 using 3-D electron microscopy (3D-EM) applied to four cortical regions in mouse. Across all cortices, we found the relative inhibitory input at the apical dendrite’s main bifurcation to be more than 3-fold stronger for layer 2 pyramidal cells than for all other pyramidal cells. Towards the distal tuft dendrites in upper layer 1, however, the relative inhibitory input was about 2-fold stronger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input density. The inhibitory to excitatory synaptic balance is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either layer 2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites in the upper layers of the cerebral cortex and point to differential computational properties of layer 2, layer 3 and layer 5 pyramidal cells in cortex.

scholarly journals Cell-type specific innervation of cortical pyramidal cells at their apical dendrites

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ali Karimi ◽  
Jan Odenthal ◽  
Florian Drawitsch ◽  
Kevin M Boergens ◽  
Moritz Helmstaedter
Keyword(s):  
Electron Microscopy ◽  
Pyramidal Cells ◽  
Inhibitory Input ◽  
Cell Type ◽  
Cell Type Specific ◽  
Cortical Regions ◽  
Apical Dendrites ◽  
Computational Properties

We investigated the synaptic innervation of apical dendrites of cortical pyramidal cells in a region between layers (L) 1 and 2 using 3-D electron microscopy applied to four cortical regions in mouse. We found the relative inhibitory input at the apical dendrite’s main bifurcation to be more than 2-fold larger for L2 than L3 and L5 thick-tufted pyramidal cells. Towards the distal tuft dendrites in upper L1, the relative inhibitory input was at least about 2-fold larger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input fraction. The inhibitory-to-excitatory synaptic ratio is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either L2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites and support differential computational properties of L2, L3 and subtypes of L5 pyramidal cells in cortex.

scholarly journals Cell Type–Specific GABAA Receptor–Mediated Tonic Inhibition in Mouse Neocortex

2008 ◽  
Vol 100 (1) ◽  
pp. 526-532 ◽  
Author(s):  
Irina Vardya ◽  
Kim R. Drasbek ◽  
Zita Dósa ◽  
Kimmo Jensen
Keyword(s):  
Fluorescent Protein ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Tonic Inhibition ◽  
Synaptic Activity ◽  
Inhibitory Input ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
Green Fluorescent

Activity of extrasynaptic GABAA receptors mediating tonic inhibition is thought to play an important role for the excitability of the mammalian cerebral cortex. However, little is known about the cell type–specific expression of tonic inhibition in particular types of cortical interneurons. Here, we used transgenic mice expressing green fluorescent protein (GFP) in somatostatin-positive (SOM) interneurons and investigated tonic inhibition in SOM interneurons versus pyramidal cells in neocortical layers 2/3. In brain slices, pyramidal cells showed a tonic current of 66 ± 19 pA in response to the δ-subunit selective GABAA agonist THIP (1 μM). On the other hand, tonic inhibition was absent in SOM interneurons (8 ± 1 pA) in response to THIP. As opposed to pyramidal cells, SOM interneurons were also insensitive to the δ-subunit preferring neurosteroid allotetrahydrodeoxycorticosterone (THDOC) (100 nM) and to elevated endogenous GABA levels in the slice. Finally, SOM interneurons received only 45% of the phasic charge transfer during GABAA receptor–mediated synaptic activity compared with pyramidal cells. Altogether, our study indicates that SOM interneurons receive relatively weak inhibitory input and cannot be brought under the influence of tonic inhibition.

scholarly journals Author response: Cell-type specific innervation of cortical pyramidal cells at their apical dendrites

2020 ◽  
Author(s):  
Ali Karimi ◽  
Jan Odenthal ◽  
Florian Drawitsch ◽  
Kevin M Boergens ◽  
Moritz Helmstaedter
Keyword(s):  
Pyramidal Cells ◽  
Author Response ◽  
Cell Type ◽  
Cell Type Specific ◽  
Apical Dendrites

scholarly journals Cell type-specific effects of isoflurane on two distinct afferent inputs to cortical layer 1

2020 ◽  
Author(s):  
Caitlin A. Murphy ◽  
Matthew I. Banks
Keyword(s):  
Ex Vivo ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Cellular Level ◽  
Cortical Layer ◽  
Cell Type ◽  
Specific Effects ◽  
Primary Mouse ◽  
Cell Type Specific ◽  
Synaptic Responses

ABSTRACTBackgroundWhile their behavioral effects are well-characterized, the mechanisms by which anaesthetics induce loss of consciousness are largely unknown. Anaesthetics may disrupt integration and propagation of information in corticothalamic networks. Recent studies have shown that isoflurane diminishes synaptic responses of thalamocortical (TC) and corticocortical (CC) afferents in a pathway-specific manner. However, whether the synaptic effects of isoflurane observed in extracellular recordings persist at the cellular level has yet to be explored.MethodsHere, we activate TC and CC layer 1 inputs in non-primary mouse neocortex in ex vivo brain slices and explore the degree to which isoflurane modulates synaptic responses in pyramidal cells and in two inhibitory cell populations, somatostatin-positive (SOM+) and parvalbumin-positive (PV+) interneurons.ResultsWe show that the effects of isoflurane on synaptic responses and intrinsic properties of these cells varies among cell type and by cortical layer. Layer 1 inputs to L4 pyramidal cells were suppressed by isoflurane at both TC and CC synapses, while those to L2/3 pyramidal cells and PV+ interneurons were not. TC inputs to SOM+ cells were rarely observed at all, while CC inputs to SOM+ interneurons were robustly suppressed by isoflurane.ConclusionsThese results suggest a mechanism by which isoflurane disrupts integration and propagation of thalamocortical and intracortical signals.

Relationship between input connectivity, morphology and orientation tuning of layer 2/3 pyramidal cells in mouse visual cortex

2020 ◽  
Author(s):  
Simon Weiler ◽  
Drago Guggiana Nilo ◽  
Tobias Bonhoeffer ◽  
Mark Hübener ◽  
Tobias Rose ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Synaptic Input ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Orientation Tuning ◽  
Inhibitory Input ◽  
Layer 2 ◽  
Dendritic Complexity ◽  
Inhibitory Synaptic Input

AbstractNeocortical pyramidal cells (PCs) display functional specializations defined by their excitatory and inhibitory circuit connectivity. For layer 2/3 (L2/3) PCs, little is known about the detailed relationship between their neuronal response properties, dendritic structure and their underlying circuit connectivity at the level of single cells. Here, we ask whether L2/3 PCs in mouse primary visual cortex (V1) differ in their functional intra- and interlaminar connectivity patterns, and how this relates to differences in visual response properties. Using a combined approach, we first characterized the orientation and direction tuning of individual L2/3 PCs with in vivo 2-photon calcium imaging. Subsequently, we performed excitatory and inhibitory synaptic input mapping of the same L2/3 PCs in brain slices using laser scanning photostimulation (LSPS).Our data from this structure-connectivity-function analysis show that the sources of excitatory and inhibitory synaptic input are different in their laminar origin and horizontal location with respect to cell position: On average, L2/3 PCs receive more inhibition than excitation from within L2/3, whereas excitation dominates input from L4 and L5. Horizontally, inhibitory input originates from locations closer to the horizontal position of the soma, while excitatory input arises from more distant locations in L4 and L5. In L2/3, the excitatory and inhibitory inputs spatially overlap on average. Importantly, at the level of individual neurons, PCs receive inputs from presynaptic cells located spatially offset, vertically and horizontally, relative to the soma. These input offsets show a systematic correlation with the preferred orientation of the postsynaptic L2/3 PC in vivo. Unexpectedly, this correlation is higher for inhibitory input offsets within L2/3 than for excitatory input offsets. When relating the dendritic complexity of L2/3 PCs to their orientation tuning, we find that sharply tuned cells have a less complex apical tree compared to broadly tuned cells. These results indicate that the spatial input offsets of the functional input connectivity are linked to orientation preference, while the orientation selectivity of L2/3 PCs is more related to the dendritic complexity.

scholarly journals State-dependent cell-type-specific membrane potential dynamics and unitary synaptic inputs in awake mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Aurélie Pala ◽  
Carl CH Petersen
Keyword(s):  
Membrane Potential ◽  
Barrel Cortex ◽  
Field Potential ◽  
Low Frequency ◽  
Inhibitory Neuron ◽  
Single Layer ◽  
Cell Type ◽  
State Dependent ◽  
Layer 2 ◽  
Cell Type Specific

The cellular and synaptic mechanisms driving cell-type-specific function during various cortical network activities and behaviors are poorly understood. Here, we targeted whole-cell recordings to two classes of inhibitory GABAergic neurons in layer 2/3 of the barrel cortex of awake head-restrained mice and correlated spontaneous membrane potential dynamics with cortical state and whisking behavior. Using optogenetic stimulation of single layer 2/3 excitatory neurons we measured unitary excitatory postsynaptic potentials (uEPSPs) across states. During active states, characterized by whisking and reduced low-frequency activity in the local field potential, parvalbumin-expressing neurons depolarized and, albeit in a small number of recordings, received uEPSPs with increased amplitude. In contrast, somatostatin-expressing neurons hyperpolarized and reduced firing rates during active states without consistent change in uEPSP amplitude. These results further our understanding of neocortical inhibitory neuron function in awake mice and are consistent with the hypothesis that distinct genetically-defined cell classes have different state-dependent patterns of activity.

scholarly journals Cell type-specific regulation of inhibition via cannabinoid type 1 receptors in rat neocortex

2013 ◽  
Vol 109 (1) ◽  
pp. 216-224 ◽  
Author(s):  
Claire L. De-May ◽  
Afia B. Ali
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Cell ◽  
Metabotropic Glutamate Receptor ◽  
Pyramidal Cells ◽  
Cb1 Receptor ◽  
Cb1 Receptors ◽  
Cell Type ◽  
Group I ◽  
Cell Type Specific

Endogenous cannabinoid type 1 (CB1) receptors demonstrate a cell type-specific expression and are potent modulators of synaptic transmission within the central nervous system. We aimed to investigate whether two classes of multipolar interneuron in the neocortex displayed a form of short-term synaptic plasticity, depolarization-induced suppression of inhibition (DSI), and whether the DSI was mediated by a common receptor. Paired whole cell recordings combined with biocytin labeling were performed between pyramidal cells and either multipolar adapting or multipolar nonadapting interneurons in layers II–IV of male Wistar rat (postnatal day 17–22) somatosensory cortex. Inhibitory postsynaptic potentials elicited by multipolar adapting interneurons were sensitive to DSI, which was blocked by the CB1 receptor antagonist AM-251 (8 μM), indicating that the suppression of inhibition was mediated by CB1 receptors. Two subpopulations of multipolar nonadapting interneuron-to-pyramidal cell connections were discovered on the basis of their susceptibility to DSI. Whereas 50% were insensitive to DSI, the remaining half were sensitive to DSI, which could not be prevented by AM-251. DSI at these connections was also insensitive to the group I (mGluRIa) and III metabotropic glutamate receptor antagonists ( RS)-1-aminoindan-1,5-dicarboxylic acid (100 μM) and ( RS)-α-cyclopropyl-4-phosphonophenylglycine (100 μM) and the group III agonist l-2-amino-4-phosphonobutanoate (50 μM). However, multipolar nonadapting interneuron-to-pyramidal cell connections were sensitive to the endocannabinoid anandamide (9 μM), mimicking the effects of DSI, which also could not be prevented by AM-251, implying a CB1 receptor-independent suppression of inhibition. These results reveal an interneuron type-specific modulation of synaptic transmission via CB receptors in the neocortex.

scholarly journals Layer 6A pyramidal cells subtypes form synaptic microcircuits with distinct functional and structural properties

2021 ◽  
Author(s):  
Danqing Yang ◽  
Guanxiao Qi ◽  
Dirk Feldmeyer
Keyword(s):  
Barrel Cortex ◽  
Dynamic Properties ◽  
Pyramidal Cells ◽  
Synaptic Connections ◽  
Cell Type ◽  
Short Term ◽  
Electrophysiological Properties ◽  
Cell Type Specific ◽  
Feedback Networks ◽  
Whole Cell Recordings

Neocortical layer 6 plays a crucial role in sensorimotor coordination and integration through functionally segregated circuits linking intracortical and subcortical areas. However, because of the high neuronal heterogeneity and sparse intralaminar connectivity data on the cell-type specific synaptic microcircuits in layer 6 remain few and far between. To address this issue, whole-cell recordings combined with morphological reconstructions have been used to identify morphoelectric types of layer 6A pyramidal cells (PCs) in rat barrel cortex. Cortico-thalamic (CT), corticocortical (CC) and cortico-claustral (CCla) pyramidal cells have been distinguished based on to their distinct dendritic and axonal morphologies as well as their different electrophysiological properties. Here we demonstrate that these three types of layer 6A pyramidal cells innervate neighboring excitatory neurons with distinct synaptic properties: CT PCs establish weak facilitating synapses to 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. Furthermore, for excitatory-inhibitory synaptic connections in layer 6 we were able to show that both the presynaptic PC type and the postsynaptic interneuron type govern the dynamic properties of the of the respective synaptic connections. We have identified a functional division of local layer 6A excitatory microcircuits which may be responsible of the differential temporal engagement of layer 6 feed-forward and feedback networks. Our results provides a basis for further investigations on the long-range cortico-cortical, cortico-thalamic and cortico-claustral pathways.

Layer- and Cell-Type-Specific Effects of Neonatal Whisker-Trimming in Adult Rat Barrel Cortex

2007 ◽  
Vol 97 (6) ◽  
pp. 4380-4385 ◽  
Author(s):  
Soo-Hyun Lee ◽  
Peter W. Land ◽  
Daniel J. Simons
Keyword(s):  
Barrel Cortex ◽  
Sensory Deprivation ◽  
Cell Type ◽  
Growth Layer ◽  
Adult Rat ◽  
Specific Effects ◽  
Layer 2 ◽  
Layer 4 ◽  
Cell Type Specific ◽  
Fast Spike

Tactile deprivation in rats produced by whisker-trimming early in life leads to abnormally robust responses of excitatory neurons in layer 4 of primary somatosensory cortex when the re-grown whiskers are stimulated. Present findings from fast-spike neurons indicate that presumed inhibitory cells fire less robustly under the same conditions. These contrasting effects may reflect altered patterns of thalamocortical input to excitatory versus inhibitory cells and/or changes in the strength of intracortical connections. Despite increased excitability of layer 4, neurons in layer 2/3 respond at control levels even after full whisker re-growth. Layer 4 synapses onto supragranular neurons may be permanently depressed as a result of neonatal sensory deprivation.

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