Millivolt-Scale DC Shifts in the Human Scalp EEG: Evidence for a  Nonneuronal Generator

Slow shifts in the human scalp-recorded EEG, including those related to changes in brain CO2 levels, have been generally assumed to result from changes in the level of tonic excitation of apical dendrites of cortical pyramidal neurons. We readdressed this issue using DC-EEG shifts elicited in healthy adult subjects by hypo- or hypercapnia. A 3-min period of hyperventilation resulted in a prompt negative shift with a rate of up to 10 μV/s at the vertex (Cz) and an extremely steep dependence (up to 100 μV/mmHg) on the end-tidal Pco2. This shift had a maximum of up to −2 mV at Cz versus the temporal derivations (T3/T4). Hyperventilation-like breathing of 5% CO2-95% O2, which does not lead to a significant hypocapnia, resulted in a near-complete block of the negative DC shift at Cz. Hypoventilation, or breathing 5% CO2 in air at normal respiratory rate, induced a positive shift. The high amplitude of the voltage gradients on the scalp induced by hyperventilation is not consistent with a neuronal origin. Instead, the present data suggest that they are generated by extracortical volume currents driven by a Pco2-dependent potential difference across epithelia separating the cerebrospinal fluid and blood. Since changes in respiratory patterns and, hence, in the level of brain Pco2, are likely to occur under a number of experimental conditions in which slow EEG responses have been reported (e.g., attention shifts, preparatory states, epileptic seizures, and hypoxic episodes), the present results call for a thorough reexamination of the mechanisms underlying scalp-recorded DC-EEG responses.

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An optogenetic method for investigating presynaptic molecular regulation

Scientific Reports ◽

10.1038/s41598-021-90244-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuni Kay ◽

Bruce E. Herring

Keyword(s):

Pyramidal Neurons ◽

Molecular Regulation ◽

Glutamatergic Synapses ◽

Experimental Conditions ◽

Regulatory Pathways ◽

Genetic Manipulations ◽

Postsynaptic Protein ◽

Presynaptic Function ◽

Synaptotagmin 1 ◽

Ca3 Pyramidal Neurons

AbstractWhile efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.

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Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice

Science Translational Medicine ◽

10.1126/scitranslmed.abc1492 ◽

2020 ◽

Vol 12 (570) ◽

pp. eabc1492

Author(s):

Lawrence S. Hsieh ◽

John H. Wen ◽

Lena H. Nguyen ◽

Longbo Zhang ◽

Stephanie A. Getz ◽

...

Keyword(s):

Mouse Model ◽

Pyramidal Neurons ◽

Focal Cortical Dysplasia ◽

Repetitive Firing ◽

Intracellular Camp ◽

Main Role ◽

Channel Activity ◽

Mechanistic Target Of Rapamycin ◽

Cortical Pyramidal Neurons ◽

Causative Link

The causative link between focal cortical malformations (FCMs) and epilepsy is well accepted, especially among patients with focal cortical dysplasia type II (FCDII) and tuberous sclerosis complex (TSC). However, the mechanisms underlying seizures remain unclear. Using a mouse model of TSC- and FCDII-associated FCM, we showed that FCM neurons were responsible for seizure activity via their unexpected abnormal expression of the hyperpolarization-activated cyclic nucleotide–gated potassium channel isoform 4 (HCN4), which is normally not present in cortical pyramidal neurons after birth. Increasing intracellular cAMP concentrations, which preferentially affects HCN4 gating relative to the other isoforms, drove repetitive firing of FCM neurons but not control pyramidal neurons. Ectopic HCN4 expression was dependent on the mechanistic target of rapamycin (mTOR), preceded the onset of seizures, and was also found in diseased neurons in tissue resected from patients with TSC and FCDII. Last, blocking HCN4 channel activity in FCM neurons prevented epilepsy in the mouse model. These findings suggest that HCN4 play a main role in seizure and identify a cAMP-dependent seizure mechanism in TSC and FCDII. Furthermore, the unique expression of HCN4 exclusively in FCM neurons suggests that gene therapy targeting HCN4 might be effective in reducing seizures in FCDII or TSC.

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Gonadal Hormones Modulate the Dendritic Spine Densities of Primary Cortical Pyramidal Neurons in Adult Female Rat

Cerebral Cortex ◽

10.1093/cercor/bhp048 ◽

2009 ◽

Vol 19 (11) ◽

pp. 2719-2727 ◽

Cited By ~ 61

Author(s):

J.-R. Chen ◽

Y.-T. Yan ◽

T.-J. Wang ◽

L.-J. Chen ◽

Y.-J. Wang ◽

...

Keyword(s):

Adult Female ◽

Dendritic Spine ◽

Pyramidal Neurons ◽

Gonadal Hormones ◽

Female Rat ◽

Cortical Pyramidal Neurons

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The Relationship between Resistance Exercise Performance and Ventilatory Efficiency after Beetroot Juice Intake in Well-Trained Athletes

Nutrients ◽

10.3390/nu13041094 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1094

Author(s):

Noemí Serra-Payá ◽

Manuel Vicente Garnacho-Castaño ◽

Sergio Sánchez-Nuño ◽

Lluís Albesa-Albiol ◽

Montserrat Girabent-Farrés ◽

...

Keyword(s):

Resistance Exercise ◽

Exercise Test ◽

Exercise Performance ◽

Beetroot Juice ◽

Experimental Conditions ◽

Double Blind ◽

Ventilatory Efficiency ◽

End Tidal ◽

Oxygen Uptake Efficiency Slope ◽

The Relationship

The assessment of ventilatory efficiency is critical to understanding the matching of ventilation (VE) and perfusion in the lungs during exercise. This study aimed to establish a causal physiological relationship between ventilatory efficiency and resistance exercise performance after beetroot juice (BJ) intake. Eleven well-trained males performed a resistance exercise test after drinking 140 mL of BJ (~12.8 mmol NO3−) or a placebo (PL). Ventilatory efficiency was assessed by the VE•VCO2−1 slope, the oxygen uptake efficiency slope and the partial pressure of end-tidal carbon dioxide (PetCO2). The two experimental conditions were controlled using a randomized, double-blind crossover design. The resistance exercise test involved repeating the same routine twice, which consisted of wall ball shots plus a full squat (FS) with a 3 min rest or without a rest between the two exercises. A higher weight lifted was detected in the FS exercise after BJ intake compared with the PL during the first routine (p = 0.004). BJ improved the VE•VCO2−1 slope and the PetCO2 during the FS exercise in the first routine and at rest (p < 0.05). BJ intake improved the VE•VCO2−1 slope and the PetCO2 coinciding with the resistance exercise performance. The ergogenic effect of BJ could be induced under aerobic conditions at rest.

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