The Effects of NMDA Receptor Blockade on Sensory-Evoked Responses in Superficial Layers of the Rat Barrel Cortex.

Transmission of excitation from L4 to L2/3 is a part of a canonical circuit of cortical sensory signal processing. While synapses from L4 to L2/3 are mediated by both AMPA and NMDA glutamate receptors, previous studies suggested that sensory-evoked excitation of neurons in supragranular layers is almost entirely mediated by NMDA receptors. Here, we readdressed this question using extracellular recordings of sensory-evoked potentials (SEPs) and multiple unit activity (MUA) in the rat barrel cortex. We found that blockade of NMDA receptors using the selective antagonist dAPV profoundly inhibited the late part of L2/3 SEP, the associated sink, and MUA response but did not affect its initial part. Our results indicate that both non-NMDA and NMDA receptors are involved in sensory signal transmission from L4 to L2/3. While non-NMDA receptors mediate fast transmission of sensory signals, NMDA-Rs are importantly involved in the generation of the late phase of the sensory-evoked response in supragranular layers.

Tuberous Breast Deformity Correction: 12-year Experience.

BACKGROUND: This article shows our 12-year experience in application of the technique of breast parenchyma modification with simultaneous augmentation on the tuberous breast. We undertook the study, and with the results of this study we can say that tuberous breast deformation is a common pathology that is caused not only by a thickening of the superficial fascia but also by breast parenchyma fibrosis. When traditional techniques without parenchyma modification are used during the surgery, it is often that patients come back to treat complications. METHODS: A total of 208 patients (414 breasts) with tuberous breast deformation treated from 2005 to 2017 were included. The mean patient age was 31 years (range, 22-53 years). A periareolar approach, vertical and horizontal glandular scoring, dual-plane pocket creation, and anatomic implants were used in all cases. RESULTS: The mean follow-up was 36 months (range, 3-144 months). Deformities of the types I-IV by Von Heimburg were corrected. The global complication rate for all patients in this study was 8.9%-1.4% had capsular contracture, 1.5% had postoperative malposition, 2% had "double bubble" , 2% had rippling, 2% had areola and nipple sensitivity disorder. CONCLUSION: The authors' experience demonstrates that the described one-stage approach combining mammary gland parenchyma modification (glandular scoring) with dual-plane pocket and anatomic implants provides satisfactory results for treatment of tubular breast deformity with minimal complications and other effects that require repeated treatment. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex.

Epipial application is one of the approaches for drug delivery into the cortex. However, passive diffusion of epipially applied drugs through the cortical depth may be slow, and different drug concentrations may be achieved at different rates across the cortical depth. Here, we explored the pharmacodynamics of the inhibitory effects of epipially applied ionotropic glutamate receptor antagonists CNQX and dAPV on sensory-evoked and spontaneous activity across layers of the cortical barrel column in urethane-anesthetized rats. The inhibitory effects of CNQX and dAPV were observed at concentrations that were an order higher than in slices in vitro, and they slowly developed from the cortical surface to depth after epipial application. The level of the inhibitory effects also followed the surface-to-depth gradient, with full inhibition of sensory evoked potentials (SEPs) in the supragranular layers and L4 and only partial inhibition in L5 and L6. During epipial CNQX and dAPV application, spontaneous activity and the late component of multiple unit activity (MUA) during sensory-evoked responses were suppressed faster than the short-latency MUA component. Despite complete suppression of SEPs in L4, sensory-evoked short-latency multiunit responses in L4 persisted, and they were suppressed by further addition of lidocaine suggesting that spikes in thalamocortical axons contribute ∼20% to early multiunit responses. Epipial CNQX and dAPV also completely suppressed sensory-evoked very fast (∼500 Hz) oscillations and spontaneous slow wave activity in L2/3 and L4. However, delta oscillations persisted in L5/6. Thus, CNQX and dAPV exert inhibitory actions on cortical activity during epipial application at much higher concentrations than in vitro, and the pharmacodynamics of their inhibitory effects is characterized by the surface-to-depth gradients in the rate of development and the level of inhibition of sensory-evoked and spontaneous cortical activity.

Direct Current Coupled Recordings of Cortical Spreading Depression Using Silicone Probes.

Electrophysiological assessment of infraslow (<0.1 Hz) brain activities such as cortical spreading depression (SD), which occurs in a number of pathologies including migraine, epilepsy, traumatic brain injury (TBI) and brain ischemia requires direct current (DC) coupled recordings of local field potentials (LFPs). Here, we describe how DC-coupled recordings can be performed using high-density iridium electrode arrays (silicone probes). We found that the DC voltage offset of the silicone probe is large and often exceeds the amplifier input range. Introduction of an offset compensation chain at the signal ground efficiently minimized the DC offsets. Silicone probe DC-coupled recordings across layers of the rat visual and barrel cortices revealed that epipial application of KCl, dura incision or pinprick TBI induced SD which preferentially propagated through the supragranular layers and further spread to the granular and infragranular layers attaining maximal amplitudes of ~-30 mV in the infragranular layers. SD at the superficial cortical layers was nearly two-fold longer than at the deep cortical layers. Continuous epipial KCl evoked multiple recurrent SDs which always started in the supragranular layers but often failed to propagate through the deeper cortical layers. Intracortical KCl injection into the infragranular layers evoked SD which also started in the supragranular layers and spread to the granular and infragranular layers, further indicating that the supragranular layers are particularly prone to SD. Thus, DC-coupled recordings with silicone probes after offset compensation can be successfully used to explore the spatial-temporal dynamics of SD and other slow brain activities.

Inhibition of Cortical Activity and Apoptosis Caused by Ethanol in Neonatal Rats In Vivo.

Alcohol consumption during pregnancy causes fetal alcohol spectrum disorder, which includes neuroapoptosis and neurobehavioral deficits. The neuroapoptotic effects of alcohol have been hypothesized to involve suppression of brain activity. However, in vitro studies suggest that ethanol acts as a potent stimulant of cortical activity. We explored the effects of alcohol (1-6 g/kg) on electrical activity in the rat somatosensory cortex in vivo at postnatal days P1-23 and compared them with its apoptotic actions. At P4-7, when the peak of alcohol-induced apoptosis was observed, alcohol strongly suppressed spontaneous gamma and spindle-bursts and almost completely silenced neurons in a dose-dependent manner. The dose-dependence of suppression of neuronal activity strongly correlated with the alcohol-induced neuroapoptosis. Alcohol also profoundly inhibited sensory-evoked bursts and suppressed motor activity, a physiological trigger of cortical activity bursts in newborns. The suppressive effects of ethanol on neuronal activity waned during the second and third postnatal weeks, when instead of silencing the cortex, alcohol evoked delta-wave electrographic activity. Thus, the effects of alcohol on brain activity are strongly age-dependent, and during the first postnatal week alcohol profoundly inhibits brain activity. Our findings suggest that the adverse effects of alcohol in the developing brain involve suppression of neuronal activity.

Sensory feedback synchronizes motor and sensory neuronal networks in the neonatal rat spinal cord.

Early stages of sensorimotor system development in mammals are characterized by the occurrence of spontaneous movements. Whether and how these movements support correlated activity in developing sensorimotor spinal cord circuits remains unknown. Here we show highly correlated activity in sensory and motor zones in the spinal cord of neonatal rats in vivo. Both during twitches and complex movements, movement-generating bursts in motor zones are followed by bursts in sensory zones. Deafferentation does not affect activity in motor zones and movements, but profoundly suppresses activity bursts in sensory laminae and results in sensorimotor uncoupling, implying a primary role of sensory feedback in sensorimotor synchronization. This is further supported by largely dissociated activity in sensory and motor zones observed in the isolated spinal cord in vitro. Thus, sensory feedback resulting from spontaneous movements is instrumental for coordination of activity in developing sensorimotor spinal cord circuits.

Isoflurane suppresses early cortical activity.

OBJECTIVE: Isoflurane and other volatile anesthetics are widely used in children to induce deep and reversible coma, but they may also exert neurotoxic actions. The effects of volatile anesthetics on the immature brain activity remain elusive, however. METHODS: The effects of isoflurane on spontaneous and sensory-evoked activity were explored using intracortical extracellular field potential and multiple unit recordings in the rat barrel cortex from birth to adulthood. RESULTS: During the first postnatal week, isoflurane suppressed cortical activity in a concentration-dependent manner. At surgical anesthesia levels (1.5-2%), isoflurane completely suppressed the electroencephalogram and silenced cortical neurons. Although sensory potentials evoked by the principal whisker deflection persisted, sensory-evoked early gamma and spindle-burst oscillations were completely suppressed by isoflurane. Isoflurane-induced burst-suppression pattern emerged during the second postnatal week and matured through the first postnatal month. Bursts in adolescent and adult rats were characterized by activation of entire cortical columns with a leading firing of infragranular neurons, and were triggered by principal and adjacent whiskers stimulation, and by auditory and visual stimuli, indicating an involvement of horizontal connections in their generation and horizontal spread. INTERPRETATION: The effects of isoflurane on cortical activity shift from total suppression of activity to burst-suppression pattern at the end of the first postnatal week. Developmental emergence of bursts likely involves a development of the intracortical short-and long-range connections. We hypothesize that complete suppression of cortical activity under isoflurane anesthesia during the first postnatal week may explain neuronal apoptosis stimulated by volatile anesthetics in the neonatal rats.