scholarly journals Distinct dendritic Ca2+ spike forms produce opposing input-output transformations in rat CA3 pyramidal cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ádám Magó ◽  
Noémi Kis ◽  
Balázs Lükő ◽  
Judit K Makara

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP), and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats, we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without bAPs, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single-action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.

2021 ◽  
Author(s):  
Ádám Magó ◽  
Noémi Kis ◽  
Balázs Lükó ◽  
Judit K Makara

Proper integration of different inputs targeting the dendritic tree of CA3 pyramidal cells (CA3PCs) is critical for associative learning and recall. Dendritic Ca2+ spikes have been proposed to perform associative computations in other PC types, by detecting conjunctive activation of different afferent input pathways, initiating afterdepolarization (ADP) and triggering burst firing. Implementation of such operations fundamentally depends on the actual biophysical properties of dendritic Ca2+ spikes; yet little is known about these properties in dendrites of CA3PCs. Using dendritic patch-clamp recordings and two-photon Ca2+ imaging in acute slices from male rats we report that, unlike CA1PCs, distal apical trunk dendrites of CA3PCs exhibit distinct forms of dendritic Ca2+ spikes. Besides ADP-type global Ca2+ spikes, a majority of dendrites expresses a novel, fast Ca2+ spike type that is initiated locally without backpropagating action potentials, can recruit additional Na+ currents, and is compartmentalized to the activated dendritic subtree. Occurrence of the different Ca2+ spike types correlates with dendritic structure, indicating morpho-functional heterogeneity among CA3PCs. Importantly, ADPs and dendritically initiated spikes produce opposing somatic output: bursts versus strictly single action potentials, respectively. The uncovered variability of dendritic Ca2+ spikes may underlie heterogeneous input-output transformation and bursting properties of CA3PCs, and might specifically contribute to key associative and non-associative computations performed by the CA3 network.


2016 ◽  
Author(s):  
Sarah Jarvis ◽  
Konstantin Nikolic ◽  
Simon R Schultz

AbstractThe mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron’s input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron’s gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells - confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain modulation.Author SummaryGain modulability indicated by dendritic morphologyPyramidal cell-like shapes optimally receptive to modulationAll dendritic subdomains required for gain modulation, partial illumination is insufficientComputational optogenetic models improve and refine experimental protocols


2005 ◽  
Vol 17 (1) ◽  
pp. 75-96 ◽  
Author(s):  
Rishikesh Narayanan ◽  
Anusha Narayan ◽  
Sumantra Chattarji

Dendritic arborization is an important determinant of single-neuron function as well as the circuitry among neurons. Dendritic trees undergo remodeling during development, aging, and many pathological conditions, with many of the morphological changes being confined to certain regions of the dendritic tree. In order to analyze the functional consequences of such region-specific dendritic remodeling, it is essential to develop techniques that can systematically manipulate three-dimensional reconstructions of neurons. Hence, in this study, we develop an algorithm that uses statistics from precise morphometric analyses to systematically remodel neuronal reconstructions. We use the distribution function of the ratio of two normal distributed random variables to specify the probabilities of remodeling along various regions of the dendritic arborization. We then use these probabilities to drive an iterative algorithm for manipulating the dendritic tree in a region-specific manner. As a test, we apply this framework to a well-characterized example of dendritic remodeling: stress-induced dendritic atrophy in hippocampal CA3 pyramidal cells. We show that our pruning algorithm is capable of eliciting atrophy that matches biological data from rodent models of chronic stress.


2000 ◽  
Vol 39 (12) ◽  
pp. 2288-2301 ◽  
Author(s):  
Nicola Berretta ◽  
Aleksej V Rossokhin ◽  
Alexander M Kasyanov ◽  
Maxim V Sokolov ◽  
Enrico Cherubini ◽  
...  

animal ◽  
2016 ◽  
Vol 10 (2) ◽  
pp. 274-282 ◽  
Author(s):  
M. van der Voort ◽  
J. Van Meensel ◽  
L. Lauwers ◽  
G. Van Huylenbroeck ◽  
J. Charlier

1957 ◽  
Vol 41 (2) ◽  
pp. 297-306 ◽  
Author(s):  
David P. C. Lloyd

Observations have been made upon a typical flexor reflex with the aim of disclosing the changes in amount, latency, and temporal configuration of reflex discharge that take place as afferent input is varied from zero to maximal for the band of cutaneous myelinated afferent fibers that extends upward from approximately 6 µ in diameter (group II fibers). Reflex threshold is reached at 6 to 12 per cent maximal afferent input. From threshold to maximal input the relation between input and amount of output is essentially linear, latency on the average decreases, the shorter central paths in general gain preference, but the known minimum pathway, one of three neurons, does not transmit unless aided by convergent activity. Flexor reflex discharge may occur in several bursts suggesting the existence of closed chain connections in the internuncial pools of the spinal cord. At any given input there is, in successively elicited reflexes, little correlation between latency and amount of discharge, at first sight a surprising result for each variable can be taken as a measure of excitability status of the motoneuron population. However, latency of discharge indicates excitability at the beginning of the reflex event whereas amount of discharge is an expression of excitability over the entire period of discharge. Given a constantly and rapidly fluctuating excitability absence of correlation between these variables would be an anticipated result.


2021 ◽  
pp. 1-37
Author(s):  
Yaqin Fan ◽  
Xile Wei ◽  
Guosheng Yi ◽  
Meili Lu ◽  
Jiang Wang ◽  
...  

Abstract An extracellular electric field (EF) induces transmembrane polarizations on extremely inhomogeneous spaces Evidence shows that EF-induced somatic polarization in pyramidal cells can modulate the neuronal input-output (I/O) function. However, it remains unclear whether and how dendritic polarization participates in the dendritic integration and contributes to the neuronal I/O function. To this end, we built a computational model of a simplified pyramidal cell with multi-dendritic tufts, one dendritic trunk, and one soma to describe the interactions among EF, dendritic integration, and somatic output, in which the EFs were modeled by inserting inhomogeneous extracellular potentials. We aimed to establish the underlying relationship between dendritic polarization and dendritic integration by analyzing the dynamics of subthreshold membrane potentials in response to AMPA synapses in the presence of constant EFs. The model-based singular perturbation analysis showed that the equilibrium mapping of a fast subsystem can serve as the asymptotic subthreshold I/O relationship for sublinear dendritic integration. This allows us to predict the tendency of EF-mediated dendritic integration by showing how EF changes modify equilibrium mapping. EF-induced hyperpolarization of distal dendrites receiving synapses inputs was found to play a key role in facilitating the AMPA receptor-evoked excitatory postsynaptic potential (EPSP) by enhancing the driving force of synaptic inputs. A significantly higher efficacy of EF modulation effect on global AMPA-type dendritic integration was found compared with local AMPA-type dendritic integration. During the generation of an action potential (AP), the relative contribution of EF-modulated dendritic integration and EF-induced somatic polarization was determined to show their collaboration in promoting or inhibiting the somatic excitability, depending on the EF polarity. These findings are crucial for understanding the EF modulation effect on neuronal computation, which provides insight into the modulation mechanism of noninvasive brain modulation.


2014 ◽  
Vol 5 ◽  
pp. JCM.S13738 ◽  
Author(s):  
Satoru Sakuma ◽  
Daisuke Tokuhara ◽  
Hiroshi Otsubo ◽  
Tsunekazu Yamano ◽  
Haruo Shintaku

Background The time course of cytokine dynamics after seizure remains controversial. Here we evaluated the changes in the levels and sites of interleukin (IL)-1β expression over time in the hippocampus after seizure. Methods Status epilepticus (SE) was induced in adult Wistar rats by means of intraperitoneal injection of kainic acid (KA). Subsequently, the time courses of cellular localization and IL-1β concentration in the hippocampus were evaluated by means of immunohistochemical and quantitative assays. Results On day 1 after SE, CA3 pyramidal cells showed degeneration and increased IL-1β expression. In the chronic phase (>7 days after SE), glial fibrillary acidic protein (GFAP)–-positive reactive astrocytes–-appeared in CA1 and became IL-1β immunoreactive. Their IL-1β immunoreactivity increased in proportion to the progressive hypertrophy of astrocytes that led to gliosis. Quantitative analysis showed that hippocampal IL-1β concentration progressively increased during the acute and chronic phases. Conclusion IL-1β affects the hippocampus after SE. In the acute phase, the main cells expressing IL-1β were CA3 pyramidal cells. In the chronic phase, the main cells expressing IL-1β were reactive astrocytes in CA1.


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