Layer-Specific Intracolumnar and Transcolumnar Functional Connectivity of Layer V Pyramidal Cells in Rat Barrel Cortex

Abstract Subcortical band heterotopia (SBH), also known as double-cortex syndrome, is a neuronal migration disorder characterized by an accumulation of neurons in a heterotopic band below the normotopic cortex. The majority of patients with SBH have mild to moderate intellectual disability and intractable epilepsy. However, it is still not clear how cortical networks are organized in SBH patients and how this abnormal organization contributes to improper brain function. In this study, cortical networks were investigated in the barrel cortex in an animal model of SBH induced by in utero knockdown of Dcx, main causative gene of this condition in human patients. When the SBH was localized below the Barrel Field (BF), layer (L) four projection to correctly positioned L2/3 pyramidal cells was weakened due to lower connectivity. Conversely, when the SBH was below an adjacent cortical region, the excitatory L4 to L2/3 projection was stronger due to increased L4 neuron excitability, synaptic strength and excitation/inhibition ratio of L4 to L2/3 connection. We propose that these developmental alterations contribute to the spectrum of clinical dysfunctions reported in patients with SBH.

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Two Populations of Layer V Pyramidal Cells of the Mouse Neocortex: Development and Sensitivity to Anesthetics

Journal of Neurophysiology ◽

10.1152/jn.00076.2005 ◽

2005 ◽

Vol 94 (5) ◽

pp. 3357-3367 ◽

Cited By ~ 50

Author(s):

Elodie Christophe ◽

Nathalie Doerflinger ◽

Daniel J. Lavery ◽

Zoltán Molnár ◽

Serge Charpak ◽

...

Keyword(s):

Action Potential ◽

Calcium Binding ◽

Pyramidal Neurons ◽

Pyramidal Cells ◽

Membrane Properties ◽

Subcortical Structures ◽

Contralateral Cortex ◽

Layer V ◽

Intrinsic Membrane Properties ◽

Two Populations

Previous studies have shown that layer V pyramidal neurons projecting either to subcortical structures or the contralateral cortex undergo different morphological and electrophysiological patterns of development during the first three postnatal weeks. To isolate the determinants of this differential maturation, we analyzed the gene expression and intrinsic membrane properties of layer V pyramidal neurons projecting either to the superior colliculus (SC cells) or the contralateral cortex (CC cells) by combining whole cell recordings and single-cell RT-PCR in acute slices prepared from postnatal day (P) 5–7 or P21–30 old mice. Among the 24 genes tested, the calcium channel subunits α1B and α1C, the protease Nexin 1, and the calcium-binding protein calbindin were differentially expressed in adult SC and CC cells and the potassium channel subunit Kv4.3 was expressed preferentially in CC cells at both stages of development. Intrinsic membrane properties, including input resistance, amplitude of the hyperpolarization-activated current, and action potential threshold, differed quantitatively between the two populations as early as from the first postnatal week and persisted throughout adulthood. However, the two cell types had similar regular action potential firing behaviors at all developmental stages. Surprisingly, when we increased the duration of anesthesia with ketamine–xylazine or pentobarbital before decapitation, a proportion of mature SC cells, but not CC cells, fired bursts of action potentials. Together these results indicate that the two populations of layer V pyramidal neurons already start to differ during the first postnatal week and exhibit different firing capabilities after anesthesia.

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Regional Differences in Late-Onset Iron Deposition, Ferritin, Transferrin, Astrocyte Proliferation, and Microglial Activation after Transient Forebrain Ischemia in Rat Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1995.27 ◽

1995 ◽

Vol 15 (2) ◽

pp. 216-226 ◽

Cited By ~ 74

Author(s):

Yoichi Kondo ◽

Norio Ogawa ◽

Masato Asanuma ◽

Zensuke Ota ◽

Akitane Mori

Keyword(s):

Rat Brain ◽

Parietal Cortex ◽

Neuronal Death ◽

Late Onset ◽

Neuronal Damage ◽

Pyramidal Cells ◽

Iron Deposition ◽

Forebrain Ischemia ◽

Transient Forebrain Ischemia ◽

Layer V

With use of iron histochemistry and immuno-histochemistry, regional changes in the appearance of iron, ferritin, transferrin, glial fibrillary acidic protein–positive astrocytes, and activated microglia were examined from 1 to 24 weeks after transient forebrain ischemia (four-vessel occlusion model) in rat brain. Expression of the C3bi receptor and the major histocompatibility complex class II antigen was used to identify microglia. Neuronal death was confirmed by hematoxylin–eosin staining only in pyramidal cells of the hippocampal CA, region, which is known as the area most vulnerable to ischemia. Perls' reaction with 3,3′-diaminobenzidine intensification revealed iron deposits in the CA, region after week 4, which gradually increased and formed clusters by week 24. Iron also deposited in layers III-V of the parietal cortex after week 8 and gradually built up as granular deposits in the cytoplasm of pyramidal cells in frontocortical layer V. An increasing astroglial reaction and the appearance of ferritin-immunopositive microglia paralleled the iron accumulation in the hippocampal CA, region, indicating that iron deposition was probably produced in the process of gliosis. Neither neuronal death nor atrophy was found in the cerebral cortex. Nevertheless, an astroglial and ferritin-immunopositive microglial reaction became evident at week 8 in the parietal cortex. On the other hand, the granular iron deposition in the pyramidal neurons of frontocortical layer V was not accompanied by any glial reaction in the chronic stage of ischemia. Three different types of iron deposition in the chronic phase after transient forebrain ischemia were shown in this study. In view of the neuronal damage caused by iron-catalyzed free radical formation, the late-onset iron deposition may be relevant to the pathogenesis of the chronic brain dysfunction seen at a late stage after cerebral ischemia.

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Chronic Suppression of Activity in Barrel Field Cortex Downregulates Sensory Responses in Contralateral Barrel Field Cortex

Journal of Neurophysiology ◽

10.1152/jn.00357.2005 ◽

2005 ◽

Vol 94 (5) ◽

pp. 3342-3356 ◽

Cited By ~ 20

Author(s):

Lu Li ◽

V. Rema ◽

Ford F. Ebner

Keyword(s):

Barrel Cortex ◽

Cortical Excitability ◽

Single Cells ◽

Cortical Function ◽

Adult Rats ◽

Strong Suppression ◽

Barrel Field ◽

Layer V ◽

Sensory Responses ◽

Prominent Response

Numerous lines of evidence indicate that neural information is exchanged between the cerebral hemispheres via the corpus callosum. Unilateral ablation lesions of barrel field cortex (BFC) in adult rats induce strong suppression of background and evoked activity in the contralateral barrel cortex and significantly delay the onset of experience-dependent plasticity. The present experiments were designed to clarify the basis for these interhemispheric effects. One possibility is that degenerative events, triggered by the lesion, degrade contralateral cortical function. Another hypothesis, alone or in combination with degeneration, is that the absence of interhemispheric activity after the lesion suppresses contralateral responsiveness. The latter hypothesis was tested by placing an Alzet minipump subcutaneously and connecting it via a delivery tube to a cannula implanted over BFC. The minipump released muscimol, a GABAA receptor agonist at a rate of 1 μl/h, onto one barrel field cortex for 7 days. Then with the pump still in place, single cells were recorded in the contralateral BFC under urethan anesthesia. The data show a ∼50% reduction in principal whisker responses (D2) compared with controls, with similar reductions in responses to the D1 and D3 surround whiskers. Despite these reductions, spontaneous firing is unaffected. Fast spiking units are more sensitive to muscimol application than regular spiking units in both the response magnitude and the center/surround ratio. Effects of muscimol are also layer specific. Layer II/III and layer IV neurons decrease their responses significantly, unlike layer V neurons that fail to show significant deficits. The results indicate that reduced activity in one hemisphere alters cortical excitability in the other hemisphere in a complex manner. Surprisingly, a prominent response decrement occurs in the short-latency (3–10 ms) component of principal whisker responses, suggesting that suppression may spread to neurons dominated by thalamocortical inputs after interhemispheric connections are inactivated. Bilateral neurological impairments have been described after unilateral stroke lesions in the clinical literature.

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Computational Modeling of Genetic Contributions to Excitability and Neural Coding in Layer V Pyramidal Cells: Applications to Schizophrenia Pathology

Frontiers in Computational Neuroscience ◽

10.3389/fncom.2019.00066 ◽

2019 ◽

Vol 13 ◽

Cited By ~ 1

Author(s):

Tuomo Mäki-Marttunen ◽

Anna Devor ◽

William A. Phillips ◽

Anders M. Dale ◽

Ole A. Andreassen ◽

...

Keyword(s):

Computational Modeling ◽

Neural Coding ◽

Pyramidal Cells ◽

Layer V ◽

Genetic Contributions

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Serotonergic Modulation of Spontaneous and Evoked Transmitter Release in Layer II Pyramidal Cells of Rat Somatosensory Cortex

Cerebral Cortex ◽

10.1093/cercor/bhaa285 ◽

2020 ◽

Author(s):

Fransiscus Adrian Agahari ◽

Christian Stricker

Keyword(s):

Somatosensory Cortex ◽

Transmitter Release ◽

Barrel Cortex ◽

Signal To Noise Ratio ◽

Pyramidal Cells ◽

Mepsc Frequency ◽

Spontaneous Noise ◽

Synaptic Dynamics ◽

Rat Somatosensory Cortex ◽

Almost All

Abstract As axons from the raphe nuclei densely innervate the somatosensory cortex, we investigated how serotonin (5-HT) modulates transmitter release in layer II pyramidal cells of rat barrel cortex. In the presence of tetrodotoxin and gabazine, 10 μM 5-HT caused a waxing and waning in the frequency of miniature excitatory postsynaptic currents (mEPSC) with no effect on amplitude. Specifically, within 15 min of recording the mEPSC frequency initially increased by 28 ± 7%, then dropped to below control (−15 ± 3%), before resurging back to 27 ± 7% larger than control. These changes were seen in 47% of pyramidal cells (responders) and were mediated by 5-HT2C receptors (5-HT2CR). Waxing resulted from phospholipase C activation, IP3 production, and Ca2+ release from presynaptic stores. Waning was prevented if PKC was blocked. In contrast, in paired recordings, the unitary EPSC amplitude was reduced by 50 ± 3% after 5-HT exposure in almost all cases with no significant effect on paired-pulse ratio and synaptic dynamics. This sustained EPSC reduction was also caused by 5-HT2R, but was mediated by presynaptic Gβγ subunits likely limiting influx through CaV2 channels. EPSC reduction, together with enhanced spontaneous noise in a restricted subset of inputs, could temporarily diminish the signal-to-noise ratio and affect the computation in the neocortical microcircuit.

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