Dataset Information

Genetic Deficiency of p53 Leads to Structural, Functional, and Synaptic Deficits in Primary Somatosensory Cortical Neurons of Adult Mice.

ABSTRACT: The tumor suppressor p53 plays a crucial role in embryonic neuron development and neurite growth, and its involvement in neuronal homeostasis has been proposed. To better understand how the lack of the p53 gene function affects neuronal activity, spine development, and plasticity, we examined the electrophysiological and morphological properties of layer 5 (L5) pyramidal neurons in the primary somatosensory cortex barrel field (S1BF) by using in vitro whole-cell patch clamp and in vivo two-photon imaging techniques in p53 knockout (KO) mice. We found that the spiking frequency, excitatory inputs, and sag ratio were decreased in L5 pyramidal neurons of p53KO mice. In addition, both in vitro and in vivo morphological analyses demonstrated that dendritic spine density in the apical tuft is decreased in L5 pyramidal neurons of p53KO mice. Furthermore, chronic imaging showed that p53 deletion decreased dendritic spine turnover in steady-state conditions, and prevented the increase in spine turnover associated with whisker stimulation seen in wildtype mice. In addition, the sensitivity of whisker-dependent texture discrimination was impaired in p53KO mice compared with wildtype controls. Together, these results suggest that p53 plays an important role in regulating synaptic plasticity by reducing neuronal excitability and the number of excitatory synapses in S1BF.

SUBMITTER: Kuang H

PROVIDER: S-EPMC9021533 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Genetic Deficiency of p53 Leads to Structural, Functional, and Synaptic Deficits in Primary Somatosensory Cortical Neurons of Adult Mice.

Kuang Haixia H Liu Tao T Jiao Cui C Wang Jianmei J Wu Shinan S Wu Jing J Peng Sicong S Davidson Andrew M AM Zeng Shelya X SX Lu Hua H Mostany Ricardo R

Frontiers in molecular neuroscience 20220407

The tumor suppressor p53 plays a crucial role in embryonic neuron development and neurite growth, and its involvement in neuronal homeostasis has been proposed. To better understand how the lack of the p53 gene function affects neuronal activity, spine development, and plasticity, we examined the electrophysiological and morphological properties of layer 5 (L5) pyramidal neurons in the primary somatosensory cortex barrel field (S1BF) by using in vitro whole-cell patch clamp and ...[more]

PMID: 35465090

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Project description:Cortical computations rely on functionally diverse and highly dynamic synapses. How their structural composition affects synaptic transmission and plasticity and whether they support functional diversity remains rather unclear. Here, synaptic boutons on layer 5B (L5B) pyramidal neurons in the adult rat barrel cortex were investigated. Simultaneous patch-clamp recordings from synaptically connected L5B pyramidal neurons revealed great heterogeneity in amplitudes, coefficients of variation (CVs), and failures (F%) of EPSPs. Quantal analysis indicated multivesicular release as a likely source of this variability. Trains of EPSPs decayed with fast and slow time constants, presumably representing release from small readily releasable (RRP; 5.40 ± 1.24 synaptic vesicles) and large recycling (RP; 74 ± 21 synaptic vesicles) pools that were independent and highly variable at individual synaptic contacts (RRP range 1.2-12.8 synaptic vesicles; RP range 3.4-204 synaptic vesicles). Most presynaptic boutons (~85%) had a single, often perforated active zone (AZ) with a ~2 to 5-fold larger pre- (0.29 ± 0.19 μm2) and postsynaptic density (0.31 ± 0.21 μm2) when compared with even larger CNS synaptic boutons. They contained 200-3400 vesicles (mean ~800). At the AZ, ~4 and ~12 vesicles were located within a perimeter of 10 and 20 nm, reflecting docked and readily releasable vesicles of a putative RRP. Vesicles (~160) at 60-200 nm constituting the structural estimate of the presumed RP were ~2-fold larger than our functional estimate of the RP although both with a high variability. The remaining constituted a presumed large resting pool. Multivariate analysis revealed two clusters of L5B synaptic boutons distinguished by the size of their resting pool. Our functional and ultrastructural analyses closely link stationary properties, temporal dynamics and endurance of synaptic transmission to vesicular content and distribution within the presynaptic boutons suggesting that functional diversity of L5B synapses is enhanced by their structural heterogeneity.

Dataset Information

Genetic Deficiency of p53 Leads to Structural, Functional, and Synaptic Deficits in Primary Somatosensory Cortical Neurons of Adult Mice.

Publications

Genetic Deficiency of p53 Leads to Structural, Functional, and Synaptic Deficits in Primary Somatosensory Cortical Neurons of Adult Mice.

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