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 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 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.

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.

scholarly journals Experience-dependent translational state defined by cell type-specific ribosome profiling

2017 ◽  
Author(s):  
Stephen M. Eacker ◽  
Khadijah Crawford ◽  
Lars Brichta ◽  
Markus Riessland ◽  
Nicholas T. Ingolia ◽  
...  
Keyword(s):  
Affinity Purification ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Ribosome Profiling ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Type ◽  
Calmodulin Binding ◽  
Cell Type Specific ◽  
Translation State

AbstractExperience-dependent neuronal activity regulates the translation of mRNA, supporting memory formation. We have developed a new method termed translating ribosome affinity purification and ribosome profiling (TRiP) which allows us to determine cell type-specific ribosome occupancy of mRNA with nucleotide resolution. Using TRiP we show that a memory-inducing experience creates a distinct translational state in mouse CA1 pyramidal cells. The experience-dependent translation state is characterized by enhanced translation of protein-coding open reading frames (ORFs) including numerous components of the actin cytoskeleton and calcium/calmodulin binding proteins, and by decreased translation of a defined subset of genes containing upstream ORFs (uORFs). Using animals heterozygous for an unphosphorylatable allele of the eukaryotic translation initiation factor 2α (eIF2α), we show that dephosphorylation of eIF2α contributes significantly to the experience-dependent translation state. These observations demonstrate that TRiP is a valuable methodology for studying physiologically relevant changes in translational state in genetically defined cell types.

scholarly journals Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gregg Wildenberg ◽  
Anastasia Sorokina ◽  
Jessica Koranda ◽  
Alexis Monical ◽  
Chad Heer ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Large Scale ◽  
Drug Exposure ◽  
Cocaine Exposure ◽  
Cell Type ◽  
Major Locus ◽  
Anatomical Plasticity ◽  
Before And After ◽  
Cell Type Specific ◽  
Serial Electron Microscopy

Dopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron microscopy to detail DA connections in the nucleus accumbens (NAc) of the mouse (Mus musculus) before and after exposure to cocaine. We find that individual DA axons contain different varicosity types based on their vesicle contents. Spatially ordering along individual axons further suggests that varicosity types are non-randomly organized. DA axon varicosities rarely make specific synapses (<2%, 6/410), but instead are more likely to form spinule-like structures (15%, 61/410) with neighboring neurons. Days after a brief exposure to cocaine, DA axons were extensively branched relative to controls, formed blind-ended ‘bulbs’ filled with mitochondria, and were surrounded by elaborated glia. Finally, mitochondrial lengths increased by ~2.2 times relative to control only in DA axons and NAc spiny dendrites after cocaine exposure. We conclude that DA axonal transmission is unlikely to be mediated via classical synapses in the NAc and that the major locus of anatomical plasticity of DA circuits after exposure to cocaine are large-scale axonal re-arrangements with correlated changes in mitochondria.

scholarly journals Corticothalamic Pathways From Layer 5: Emerging Roles in Computation and Pathology

2021 ◽  
Vol 15 ◽  
Author(s):  
Rebecca A. Mease ◽  
Antonio J. Gonzalez
Keyword(s):  
Single Neuron ◽  
Brain Regions ◽  
Cortical Layer ◽  
Cell Type ◽  
First Order ◽  
Sensory Modalities ◽  
Important Pathway ◽  
Cell Type Specific ◽  
Computational Properties

Large portions of the thalamus receive strong driving input from cortical layer 5 (L5) neurons but the role of this important pathway in cortical and thalamic computations is not well understood. L5-recipient “higher-order” thalamic regions participate in cortico-thalamo-cortical (CTC) circuits that are increasingly recognized to be (1) anatomically and functionally distinct from better-studied “first-order” CTC networks, and (2) integral to cortical activity related to learning and perception. Additionally, studies are beginning to elucidate the clinical relevance of these networks, as dysfunction across these pathways have been implicated in several pathological states. In this review, we highlight recent advances in understanding L5 CTC networks across sensory modalities and brain regions, particularly studies leveraging cell-type-specific tools that allow precise experimental access to L5 CTC circuits. We aim to provide a focused and accessible summary of the anatomical, physiological, and computational properties of L5-originating CTC networks, and outline their underappreciated contribution in pathology. We particularly seek to connect single-neuron and synaptic properties to network (dys)function and emerging theories of cortical computation, and highlight information processing in L5 CTC networks as a promising focus for computational studies.

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