scholarly journals Using computer simulations to determine the limitations of dynamic clamp stimuli applied at the soma in mimicking distributed conductance sources

2011 ◽  
Vol 105 (5) ◽  
pp. 2610-2624 ◽  
Author(s):  
Risa J. Lin ◽  
Dieter Jaeger
Keyword(s):  
Computer Simulations ◽  
Dendritic Tree ◽  
Cell Types ◽  
Cerebellar Nuclei ◽  
Realistic Model ◽  
Pattern Generation ◽  
Synaptic Activity ◽  
Dynamic Clamp ◽  
Neuronal Responses ◽  
Cell Type

In previous studies we used the technique of dynamic clamp to study how temporal modulation of inhibitory and excitatory inputs control the frequency and precise timing of spikes in neurons of the deep cerebellar nuclei (DCN). Although this technique is now widely used, it is limited to interpreting conductance inputs as being location independent; i.e., all inputs that are biologically distributed across the dendritic tree are applied to the soma. We used computer simulations of a morphologically realistic model of DCN neurons to compare the effects of purely somatic vs. distributed dendritic inputs in this cell type. We applied the same conductance stimuli used in our published experiments to the model. To simulate variability in neuronal responses to repeated stimuli, we added a somatic white current noise to reproduce subthreshold fluctuations in the membrane potential. We were able to replicate our dynamic clamp results with respect to spike rates and spike precision for different patterns of background synaptic activity. We found only minor differences in the spike pattern generation between focal or distributed input in this cell type even when strong inhibitory or excitatory bursts were applied. However, the location dependence of dynamic clamp stimuli is likely to be different for each cell type examined, and the simulation approach developed in the present study will allow a careful assessment of location dependence in all cell types.

Physiology of the A1 amacrine: A spiking, axon-bearing interneuron of the macaque monkey retina

1997 ◽  
Vol 14 (3) ◽  
pp. 507-522 ◽  
Author(s):  
Donna K. Stafford ◽  
Dennis M. Dacey
Keyword(s):  
Receptive Field ◽  
Amacrine Cell ◽  
Dendritic Tree ◽  
Amacrine Cells ◽  
Cell Types ◽  
Macaque Monkey ◽  
Cell Type ◽  
Slow Potential ◽  
Spike Discharge

AbstractWe characterized the light response, morphology, and receptive-field structure of a distinctive amacrine cell type (Dacey, 1989), termed here the Al amacrine, by applying intracellular recording and staining methods to the macaque monkey retina in vitro. A1 cells show two morphologically distinct components: a highly branched and spiny dendritic tree, and a more sparsely branched axon-like tree that arises from one or more hillock-like structures near the soma and extends for several millimeters beyond the dendritic tree. Intracellular injection of Neurobiotin reveals an extensive and complex pattern of tracer coupling to neighboring A1 amacrine cells, to two other amacrine cell types, and to a single ganglion cell type. The A1 amacrine is an ON-OFF cell, showing a large (10–20 mV) transient depolarization at both onset and offset of a photopic, luminance modulated stimulus. A burst of fast, large-amplitude (Σ60 mV) action potentials is associated with the depolarizations at both the ON and OFF phase of the response. No evidence was found for an inhibitory receptive-field surround. The spatial extent of the ON-OFF response was mapped by measuring the strength of the spike discharge and/or the amplitude of the depolarizing slow potential as a function of the position of a bar or spot of light within the receptive field. Receptive fields derived from the slow potential and associated spike discharge corresponded in size and shape. Thus, the amplitude of the slow potential above spike threshold was well encoded as spike frequency. The diameter of the receptive field determined from the spike discharge was Σ10% larger than the spiny dendritic field. The correspondence in size between the spiking receptive field and the spiny dendritic tree suggests that light driven signals are conducted to the soma from the dendritic tree but not from the axon-like arbor. The function of the axon-like component is unknown but we speculate that it serves a classical output function, transmitting spikes distally from initiation sites near the soma.

scholarly journals Rapid propagation of membrane tension at a presynaptic terminal

2021 ◽  
Author(s):  
Carolina Gomis Perez ◽  
Natasha R Dudzinski ◽  
Mason Rouches ◽  
Benjamin Machta ◽  
David Zenisek ◽  
...  
Keyword(s):  
Chromaffin Cells ◽  
Cell Types ◽  
Synaptic Activity ◽  
Membrane Tension ◽  
Cell Type ◽  
Membrane Flow ◽  
Common View ◽  
The Common ◽  
Adrenal Chromaffin ◽  
Stimulation Of

Many cellular activities, such as cell migration1, cell division, signaling, infection, phagocytosis and exo-endocytosis, generate membrane tension gradients that in turn regulate them. Moreover, membrane flows, which are driven by tension gradients, can limit exo-endocytosis coupling in space and time, as net membrane flow from exocytic to endocytic sites is required to maintain membrane homeostasis. However, there is controversy over how rapidly plasma membrane flows can relax tension gradients; contrary to the common view, recent work showed membrane tension does not equilibrate in several cell types. Here we show membrane tension can propagate rapidly or slowly, spanning orders of magnitude in speed, depending on cell type. In a neuronal terminal specialized for rapid synaptic vesicle turnover and where exo-endocytosis events occur at distinct loci, membrane tension equilibrates within seconds. By contrast, membrane tension does not propagate in neuroendocrine adrenal chromaffin cells secreting catecholamines. Thus, slow membrane flow and tension equilibration may confine exo- and exocytosis to the same loci. Stimulation of exocytosis causes a rapid, global decrease in the synaptic terminal membrane tension, which recovers slowly due to endocytosis. Our results demonstrate membrane tension propagates rapidly at neuronal terminals and varies during synaptic activity, likely contributing to exo-endocytosis coupling.

scholarly journals Diverse inhibitory projections from the cerebellar interposed nucleus

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elena N Judd ◽  
Samantha M Lewis ◽  
Abigail L Person
Keyword(s):  
Inferior Olive ◽  
Cell Types ◽  
Cerebellar Nuclei ◽  
Inhibitory Neurons ◽  
Cell Type ◽  
Functional Specificity ◽  
Functional Roles ◽  
Interposed Nucleus ◽  
Parallel Circuit ◽  
Cell Type Specific

The cerebellum consists of parallel circuit modules that contribute to diverse behaviors, spanning motor to cognitive. Recent work employing cell-type-specific tracing has identified circumscribed output channels of the cerebellar nuclei (CbN) that could confer tight functional specificity. These studies have largely focused on excitatory projections of the CbN, however, leaving open the question of whether inhibitory neurons also constitute multiple output modules. We mapped output and input patterns to intersectionally restricted cell types of the interposed and adjacent interstitial nuclei in mice. In contrast to the widespread assumption of primarily excitatory outputs and restricted inferior olive-targeting inhibitory output, we found that inhibitory neurons from this region ramified widely within the brainstem, targeting both motor- and sensory-related nuclei, distinct from excitatory output targets. Despite differences in output targeting, monosynaptic rabies tracing revealed largely shared afferents to both cell classes. We discuss the potential novel functional roles for inhibitory outputs in the context of cerebellar theory.

scholarly journals Cerebellar nuclei evolved by repeatedly duplicating a conserved cell type set

2020 ◽  
Author(s):  
Justus M Kebschull ◽  
Noam Ringach ◽  
Ethan B Richman ◽  
Drew Friedmann ◽  
Sai Saroja Kolluru ◽  
...  
Keyword(s):  
Brain Region ◽  
Cell Types ◽  
Cerebellar Nuclei ◽  
Inhibitory Neurons ◽  
Cell Type ◽  
Cell Class ◽  
Single Nucleus ◽  
Entire Cell ◽  
Region Evolution

AbstractHow have complex brains evolved from simple circuits? Here we investigated brain region evolution at cell type resolution in the cerebellar nuclei (CN), the output structures of the cerebellum. Using single-nucleus RNA sequencing in mice, chickens, and humans, as well as STARmap spatial transcriptomic analysis and whole-CNS projection tracing in mice, we identified a conserved cell type set containing two classes of region-specific excitatory neurons and three classes of region-invariant inhibitory neurons. This set constitutes an archetypal CN that was repeatedly duplicated to form new regions. Interestingly, the excitatory cell class that preferentially funnels information to lateral frontal cortices in mice becomes predominant in the massively expanded human Lateral CN. Our data provide the first characterization of CN transcriptomic cell types in three species and suggest a model of brain region evolution by duplication and divergence of entire cell type sets.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

scholarly journals Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 634
Author(s):  
Bailee H. Sliker ◽  
Paul M. Campbell
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Fibroblast Activation Protein ◽  
Cancer Associated Fibroblasts ◽  
Cell Type ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
New Research ◽  
Tumor Types

Tumors are composed of not only epithelial cells but also many other cell types that contribute to the tumor microenvironment (TME). Within this space, cancer-associated fibroblasts (CAFs) are a prominent cell type, and these cells are connected to an increase in tumor progression as well as alteration of the immune landscape present in and around the tumor. This is accomplished in part by their ability to alter the presence of both innate and adaptive immune cells as well as the release of various chemokines and cytokines, together leading to a more immunosuppressive TME. Furthermore, new research implicates CAFs as players in immunotherapy response in many different tumor types, typically by blunting their efficacy. Fibroblast activation protein (FAP) and transforming growth factor β (TGF-β), two major CAF proteins, are associated with the outcome of different immunotherapies and, additionally, have become new targets themselves for immune-based strategies directed at CAFs. This review will focus on CAFs and how they alter the immune landscape within tumors, how this affects response to current immunotherapy treatments, and how immune-based treatments are currently being harnessed to target the CAF population itself.

scholarly journals Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amitava Basu ◽  
Vijay K. Tiwari
Keyword(s):  
Regenerative Medicine ◽  
Cell Types ◽  
Direct Conversion ◽  
Cellular Reprogramming ◽  
Specific Cell ◽  
Cell Type ◽  
Pathological Conditions ◽  
Gene Regulatory ◽  
Induced Pluripotent ◽  
And Function

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.

scholarly journals Connectivity characterization of the mouse basolateral amygdalar complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  
Keyword(s):  
Granular Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Cell Type ◽  
Connectivity Map ◽  
Analysis Techniques ◽  
Domain Specific ◽  
Cell Type Specific ◽  
Unique Domain

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

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