In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons

ABSTRACT Dbl is the prototype of a large family of GDP-GTP exchange factors for small GTPases of the Rho family. In vitro, Dbl is known to activate Rho and Cdc42 and to induce a transformed phenotype. Dbl is specifically expressed in brain and gonads, but its in vivo functions are largely unknown. To assess its role in neurogenesis and gametogenesis, targeted deletion of the murine Dbl gene was accomplished in embryonic stem cells. Dbl-null mice are viable and did not show either decreased reproductive performances or obvious neurological defects. Histological analysis of mutant testis showed normal morphology and unaltered proliferation and survival of spermatogonia. Dbl-null brains indicated a correct disposition of the major neural structures. Analysis of cortical stratification indicated that Dbl is not crucial for neuronal migration. However, in distinct populations of Dbl-null cortical pyramidal neurons, the length of dendrites was significantly reduced, suggesting a role for Dbl in dendrite elongation.

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Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons

Cell Reports ◽

10.1016/j.celrep.2021.109972 ◽

2021 ◽

Vol 37 (6) ◽

pp. 109972

Author(s):

Joshua B. Melander ◽

Aran Nayebi ◽

Bart C. Jongbloets ◽

Dale A. Fortin ◽

Maozhen Qin ◽

...

Keyword(s):

Pyramidal Neurons ◽

Excitatory Synapses ◽

Cortical Pyramidal Neurons

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Activation of Serotonin Receptors Modulates Synaptic Transmission in Rat Cerebral Cortex

Journal of Neurophysiology ◽

10.1152/jn.1999.82.6.2989 ◽

1999 ◽

Vol 82 (6) ◽

pp. 2989-2999 ◽

Cited By ~ 150

Author(s):

Fu-Ming Zhou ◽

John J. Hablitz

Keyword(s):

Cerebral Cortex ◽

Pyramidal Neurons ◽

Short Pulse ◽

Inhibitory Neurons ◽

Cellular Mechanisms ◽

Postsynaptic Currents ◽

Cortical Pyramidal Neurons ◽

Immunohistochemical Studies

The cerebral cortex receives an extensive serotonergic (5-hydroxytryptamine, 5-HT) input. Immunohistochemical studies suggest that inhibitory neurons are the main target of 5-HT innervation. In vivo extracellular recordings have shown that 5-HT generally inhibited cortical pyramidal neurons, whereas in vitro studies have shown an excitatory action. To determine the cellular mechanisms underlying the diverse actions of 5-HT in the cortex, we examined its effects on cortical inhibitory interneurons and pyramidal neurons. We found that 5-HT, through activation of 5-HT2A receptors, induced a massive enhancement of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons, lasting for ∼6 min. In interneurons, this 5-HT-induced enhancement of sIPSCs was much weaker. Activation of 5-HT2Areceptors also increased spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons. This response desensitized less and at a slower rate. In contrast, 5-HT slightly decreased evoked IPSCs (eIPSCs) and eEPSCs. In addition, 5-HT via 5-HT3 receptors evoked a large and rapidly desensitizing inward current in a subset of interneurons and induced a transient enhancement of sIPSCs. Our results suggest that 5-HT has widespread effects on both interneurons and pyramidal neurons and that a short pulse of 5-HT is likely to induce inhibition whereas the prolonged presence of 5-HT may result in excitation.

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Author response for "In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice"

10.1002/jnr.24676/v2/response1 ◽

2020 ◽

Author(s):

Kevin C. Stieger ◽

James R. Eles ◽

Kip A. Ludwig ◽

Takashi D. Y. Kozai

Keyword(s):

Pyramidal Neurons ◽

Author Response ◽

Calcium Dynamics ◽

Male Mice

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Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1615330113 ◽

2016 ◽

Vol 113 (46) ◽

pp. E7287-E7296 ◽

Cited By ~ 76

Author(s):

Abhishek Banerjee ◽

Rajeev V. Rikhye ◽

Vincent Breton-Provencher ◽

Xin Tang ◽

Chenchen Li ◽

...

Keyword(s):

Rett Syndrome ◽

Time Course ◽

Pyramidal Neurons ◽

Reversal Potential ◽

Mutant Mice ◽

Loss Of Function ◽

Cortical Circuits ◽

Recombinant Human Insulin ◽

Cortical Pyramidal Neurons

Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging. Targeted recordings reveal that parvalbumin-expressing (PV+) interneurons in mutant mice have reduced responses. PV-specific MeCP2 deletion alone recapitulates effects of global MeCP2 deletion on cortical circuits, including reduced pyramidal neuron responses and reduced response reliability and selectivity. Furthermore, MeCP2 mutant mice show reduced expression of the cation-chloride cotransporter KCC2 (K+/Cl− exporter) and a reduced KCC2/NKCC1 (Na+/K+/Cl− importer) ratio. Perforated patch recordings demonstrate that the reversal potential for GABA is more depolarized in mutant mice, but is restored by application of the NKCC1 inhibitor bumetanide. Treatment with recombinant human insulin-like growth factor-1 restores responses of PV+ and pyramidal neurons and increases KCC2 expression to normalize the KCC2/NKCC1 ratio. Thus, loss of MeCP2 in the brain alters both excitation and inhibition in brain circuits via multiple mechanisms. Loss of MeCP2 from a specific interneuron subtype contributes crucially to the cell-specific and circuit-wide deficits of RTT. The joint restoration of inhibition and excitation in cortical circuits is pivotal for functionally correcting the disorder.

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