Biology subjects

Makara, J. K.

Publications and source records attributed to Makara, J. K..

3 recordsLinked to original sources

bioRxiv2024

Diverse calcium dynamics underlie place field formation in hippocampal CA1 pyramidal cells

Every explored environment is represented in the hippocampus by the activity of distinct populations of pyramidal cells (PCs) that typically fire at specific locations called their place fields (PFs). New PFs are constantly born even in familiar surroundings (during representational drift), and many rapidly emerge when the animal explores a new or altered environment (during global or partial remapping). Behavioral time scale synaptic plasticity (BTSP), a plasticity mechanism based on prolonged somatic action potential (AP) bursts induced by dendritic Ca2+/NMDA plateau potentials, was recently proposed as the main cellular mechanism underlying new PF formations (PFF), but it is unclear whether burst-associated large somatic [Ca2+] transients are always necessary and/or sufficient for PFF. To address this issue, here we performed in vivo two-photon [Ca2+] imaging of hippocampal CA1 PCs in head-restrained mice to investigate somatic [Ca2+] dynamics underlying PFFs in familiar and novel virtual environments. Our results demonstrate that although many PFs are formed by BTSP-like events, PFs also emerge with initial [Ca2+] dynamics that do not match any of the characteristics of BTSP. BTSP and non-BTSP-like new PFFs occur spontaneously in familiar environments, during neuronal representational switches and instantaneously in new environments. Our data also reveal that solitary [Ca2+] transients with larger amplitudes than those evoking BTSP-like PFFs, frequently occur without inducing PFs, demonstrating that large [Ca2+] transients per se are not sufficient for PFF.

neuroscience↗

bioRxiv2021

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

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.

neuroscience↗

bioRxiv2019

Impact of functional synapse clusters on neuronal response selectivity.

Clustering of functionally similar synapses in dendrites is thought to affect input-output transformation by inducing dendritic nonlinearities. However, neither the in vivo impact of synaptic clusters on somatic membrane potential (sVm), nor the rules of cluster formation are elucidated. We developed a computational approach to measure the effect of functional synaptic clusters on sVm response of biophysical model CA1 and L2/3 pyramidal neurons to behaviorally relevant in vivo-like inputs. Large-scale dendritic spatial inhomogeneities in synaptic tuning properties did influence sVm, but small synaptic clusters appearing randomly with unstructured connectivity did not. With structured connectivity, ~10-20 synapses per cluster was optimal for clustering-based tuning, but larger responses were achieved by 2-fold potentiation of the same synapses. We further show that without nonlinear amplification of the effect of random clusters, action potential-based, global plasticity rules can not generate functional clustering. Our results suggest that clusters likely form via local synaptic interactions, and have to be moderately large to impact sVm responses.

neuroscience↗