Saccadic inhibition during free viewing in macaque monkeys.

Through the process of saccadic inhibition, visual events briefly suppress eye movements including microsaccades. In humans, saccadic inhibition has been shown to occur in response to the presentation of parafoveal or peripheral visual distractors during fixation and target-directed saccades and to physical changes of behaviorally relevant visual objects. In monkeys performing tasks that controlled eye movements, saccadic inhibition of microsaccades and target-directed saccades has been shown. Using eye data from three previously published studies, we investigated how saccade rate changed while monkeys were presented with visual stimuli under conditions with loose or no viewing demands. In two conditions, animals passively sat while an LED lamp flashed or screen-wide images appeared in front of them. In the third condition, images were repeated semiperiodically while animals had to maintain their gaze within a wide rectangular area and detect oddballs. Despite animals not being required to maintain fixation or make saccades to particular targets, the onset of visual events led to a temporary reduction of saccade rate across all conditions. Interestingly, saccadic inhibition was found at image offsets as well. These results show that saccadic inhibition occurs in monkeys during free viewing.NEW & NOTEWORTHY We investigated the time courses of saccade rate following visual stimuli during three conditions of free viewing in macaque monkeys. Under all conditions, saccade rate decreased transiently after the onset of visual stimuli. These results suggest that saccadic inhibition occurs during free viewing.

Cross Laminar Traveling Components of Field Potentials due to Volume Conduction of Non-Traveling Neuronal Activity in Macaque Sensory Cortices.

Field potentials (FPs) reflect neuronal activities in the brain, and often exhibit traveling peaks across recording sites. While traveling FPs are interpreted as propagation of neuronal activity, not all studies directly reveal such propagating patterns of neuronal activation. Neuronal activity is associated with transmembrane currents that form dipoles and produce negative and positive fields. Thereby, FP components reverse polarity between those fields and have minimal amplitudes at the center of dipoles. Although their amplitudes could be smaller, FPs are never flat even around these reversals. What occurs around the reversal has not been addressed explicitly, although those are rationally in the middle of active neurons. We show that sensory FPs around the reversal appeared with peaks traveling across cortical laminae in macaque sensory cortices. Interestingly, analyses of current source density did not depict traveling patterns but lamina-delimited current sinks and sources. We simulated FPs produced by volume conduction of a simplified 2 dipoles' model mimicking sensory cortical laminar current source density components. While FPs generated by single dipoles followed the temporal patterns of the dipole moments without traveling peaks, FPs generated by concurrently active dipole moments appeared with traveling components in the vicinity of dipoles by superimposition of individually non-traveling FPs generated by single dipoles. These results indicate that not all traveling FP are generated by traveling neuronal activity, and that recording positions need to be taken into account to describe FP peak components around active neuronal populations.SIGNIFICANCE STATEMENT Field potentials (FPs) generated by neuronal activity in the brain occur with fields of opposite polarity. Likewise, in the cerebral cortices, they have mirror-imaged waveforms in upper and lower layers. We show that FPs appear like traveling across the cortical layers. Interestingly, the traveling FPs occur without traveling components of current source density, which represents transmembrane currents associated with neuronal activity. These seemingly odd findings are explained using current source density models of multiple dipoles. Concurrently active, non-traveling dipoles produce FPs as mixtures of FPs produced by individual dipoles, and result in traveling FP waveforms as the mixing ratio depends on the distances from those dipoles. The results suggest that not all traveling FP components are associated with propagating neuronal activity.

Magnifying Traveling Waves on the Scalp.

Traveling waves appear in various signals that measure neuronal activity. Some signals measured in animals have singles-cell resolution and directly point to neuronal activity. In those cases, activation of distributed neurons forms a wave front, and the front propagates across the cortical surface. Other signals are variants of neuroelectric potentials, i.e. electroencephalography, electrocorticography and field potentials. Instead of having fine spatial resolution, these signals reflect the activity of neuronal populations via volume conduction (VC). Sources of traveling waves in neuroelectric potentials have not been well addressed so far. As animal studies show propagating activation of neurons that spread in measured areas, it is often considered that neuronal activations during scalp waves have similar trajectories of activation, spreading like scalp waves. However, traveling waves on the scalp differ from those found directly on the cortical surface in several dimensions: traveling velocity, traveling distance and areal size occupied by single polarity. We describe that the simplest sources can produce scalp waves with perceived spatial dimensions which are actually a magnification of neuronal activity emanating from local sources due to VC. This viewpoint is not a rigorous proof of our magnification concept. However, we suggest the possibility that the actual dimensions of neuronal activity producing traveling waves is not as large as the dimension of the traveling waves.

The effects of felbamate on appetitive and aversive instrumental learning in adult rats.

Antiepileptic medications are the frontline treatment for seizure conditions but are not without cognitive side effects. Previously, our laboratory reported learning deficits in phenytoin-, carbamazepine-, and valproate-treated rats. In the present experiment, the effects of felbamate (FBM) have been compared to water-treated controls (controls) using the same instrumental training tasks employed here. Rats treated with FBM displayed a deficit in acquiring a tone-signaled avoidance response, relative to controls, but this was true only if they had no prior appetitive experience. Terminal avoidance behavior was equivalent to healthy controls. In contrast, the FBM-treated rats showed enhanced acquisition of the avoidance response relative to controls when given the benefit of prior experience in the appetitive condition. Relative to animals treated with phenytoin, carbamazepine, or valproate, FBM-treated rats showed the lowest overall pattern of deficits using these instrumental learning tasks. While FBM treatment has been severely restricted because of rather low risks of serious medical side effects, we suggest that the risks are not substantially higher than those shown to exist for phenytoin, carbamazepine, or valproate. As psychologists, we further suggest that negative cognitive deficits associated with these various drugs, along with their quality-of-life costs, are of relevance in the design of treatment strategies for individuals with seizure disorders.

The effects of ethosuximide on aversive instrumental learning in adult rats.

Antiepileptic medications are the frontline treatment for seizure conditions but are not without cognitive side effects. Previously, our laboratory reported learning deficits in phenytoin-, carbamazepine-, valproic acid-, and felbamate-treated rats. In this experiment, the effects found in ethosuximide (ETH)-treated rats have been compared with those in water-treated controls (controls) using the same instrumental training tasks. Rats treated with ETH did not display any performance deficits in any of the conditions tested relative to controls. These animals showed more rapid acquisition of the avoidance response than the control animals but only when they had prior experience in the appetitive condition. Of the drugs tested to date with these learning paradigms, ETH is the only one that did not impair performance relative to controls in any condition tested. Moreover, in comparison with rats treated with valproic acid, the only other available compound commonly recommended for the treatment of absence seizures, ETH-treated rats show substantially higher performance.

Reconciling homeostatic and use-dependent plasticity in the context of somatosensory deprivation.

The concept of homeostatic plasticity postulates that neurons maintain relatively stable rates of firing despite changing inputs. Homeostatic and use-dependent plasticity mechanisms operate concurrently, although they have different requirements for induction. Depriving central somatosensory neurons of their primary activating inputs reduces activity and results in compensatory changes that favor excitation. Both a reduction of GABAergic inhibition and increase in glutamatergic excitatory transmission are observed in input-deprived cortex. Topographic reorganization of the adult somatosensory cortex is likely driven by both homeostatic and use-dependent mechanisms. Plasticity is induced by changes in the strengths of synaptic inputs, as well as changes in temporal correlation of neuronal activity. However, there is less certainty regarding the in vivo contribution of homeostatic mechanisms as in vitro experiments rely on manipulations that create states that do not normally occur in the living nervous system. Homeostatic plasticity seems to occur, but more in vivo research is needed to determine mechanisms. In vitro research is also needed but should better conform to conditions that might occur naturally in vivo.

Comparison of Scalp ERP to Faces in Macaques and Humans.

Face recognition is an essential activity of social living, common to many primate species. Underlying processes in the brain have been investigated using various techniques and compared between species. Functional imaging studies have shown face-selective cortical regions and their degree of correspondence across species. However, the temporal dynamics of face processing, particularly processing speed, are likely different between them. Across sensory modalities activation of primary sensory cortices in macaque monkeys occurs at about 3/5 the latency of corresponding activation in humans, though this human simian difference may diminish or disappear in higher cortical regions. We recorded scalp event-related potentials (ERPs) to presentation of faces in macaques and estimated the peak latency of ERP components. Comparisons of latencies between macaques (112 ms) and humans (192 ms) suggested that the 3:5 ratio could be preserved in higher cognitive regions of face processing between those species.

Female rat transcriptome response to infraorbital nerve transection differs from that of males: RNA-seq.

The effects of infraorbital nerve (ION) transection on gene expression in the adult female rat barrel cortex were investigated using RNA sequencing. After a 24-hour survival duration, 28 genes were differentially regulated by ION transection. Differentially expressed genes suggest microglial activity, increased retrograde ciliary transport, and a decrease in inhibition. These changes may be functionally comparable to changes in the male barrel cortex, where changes in genes related to morphology, neuronal activity, and neuronal excitability were observed. However, the patterns in changes in gene expression are vastly different between male and female rats. The results strongly caution against the practice of generalizing data from one sex to both sexes. This cautionary note has potentially profound implications for a range of research lines, including substance abuse and stress, both research domains in which subjects have been predominantly males. Future research needs to employ sex as a classification variable, as sex differences can generally be expected. Future research is also needed to confirm that changes in gene expression observed with RNA-seq correlate with changes in protein expression. J. Comp. Neurol. 525:140-150, 2017. © 2016 Wiley Periodicals, Inc.

Transcriptome response to infraorbital nerve transection in the gonadally intact male rat barrel cortex: RNA-seq.

The effects of infraorbital nerve (ION) transection on gene expression in the adult male rat barrel cortex were investigated using RNA sequencing. After a 24-hour survival duration, 98 genes were differentially regulated by ION transection. Differentially expressed genes suggest changes in neuronal activity, excitability, and morphology. The production of mRNA for neurotrophins, including brain-derived neurotrophin factor (BNDF), was decreased following ION transection. Several potassium channels showed decreased mRNA production, whereas a sodium channel (Na(V)ß4) associated with burst firing showed increased mRNA production. The results may have important implications for phantom-limb pain and complex regional pain syndrome. Future experiments should determine the extent to which changes in RNA result in changes in protein expression, in addition to utilizing laser capture microdissection techniques to differentiate between neuronal and glial cells.

The effects of valproic acid on appetitive and aversive instrumental learning in adult rats.

Antiepileptic medications are the frontline treatment for seizure conditions. However, these medications are not without cognitive side effects. Previously, our laboratory reported learning deficits in phenytoin and carbamazepine-treated rats. In the experiment reported here, the effects of valproic acid (VPA) have been studied using the same instrumental training tasks. VPA-treated rats displayed a severe deficit in acquiring a tone-signaled avoidance response. This deficit was attenuated in animals that had prior training in an appetitive context. Thus, this deficit is specific to learning in an aversive context, and does not result from difficulties in transferring associations from an appetitive to aversive context. Learning transfer deficits were previously observed in rats treated with phenytoin, and to a lesser extent, carbamazepine. On the other hand, rats treated with VPA fail to suppress inappropriate responsiveness across aversive training whether they had undergone prior appetitive training or not.

Response of the regulatory oscillatory behavior of copperII-containing ECTO-NOX proteins and of CuIICl2 in solution to electromagnetic fields.

A family of cell surface and growth-related proteins, designated ECTO-NOX proteins, carry out both copper-dependent NADH and hydroquinone oxidation and protein disulfide-thiol interchange. The two activities they catalyze alternate to generate a regular period of 24min in length for the constitutive CNOX. Unexpectedly, Cu(II) salts alone in solution catalyze NADH (or hydroquinone) oxidation with a similar oscillatory pattern. Both patterns consist of five maxima, two of which at physiological temperatures are separated by an interval of 6min and three of which are separated by intervals of 4.5min [6min+4 (4.5min)]. EXAFS and infrared spectroscopic measurements on pure water have shown previously that the ratios of ortho and para isomers of the hydrogen atoms of water occur on a similar time scale and produce regular patterns of unequally spaced oscillations similar to those observed with ECTO-NOX proteins and Cu(II)Cl(2) solutions. Here, we provide results from Cu(II)Cl(2) solutions that demonstrate that ECTO-NOX-/Cu(II)-catalyzed oscillations in NADH oxidation are phased by exposure to low frequency electromagnetic fields.

Periodic fluctuations in oxygen consumption comparing HeLa (cancer) and CHO (non-cancer) cells and response to external NAD(P)+/NAD(P)H.

Oxygen consumption in the presence of cyanide was utilized as a measure of plasma membrane electron transport in Chinese hamster ovary (CHO) and human cervical carcinoma (HeLa) cell lines. Both intact cells and isolated plasma membranes carry cyanide-insensitive NADH(P)H oxidases at their external membrane surfaces (designated ECTO-NOX proteins). Regular oscillatory patterns of oxygen consumption with period lengths characteristic of those observed for rates of NADH oxidation by ECTO-NOX proteins were observed to provide evidence for transfer of protons and electrons to reduce oxygen to water. The oscillations plus the resistance to inhibition by cyanide identify the bulk of the oxygen consumption as due to ECTO-NOX proteins. With intact CHO cells, oxygen consumption was enhanced by but not dependent upon external NAD(P)H addition. With intact HeLa cells, oxygen consumption was inhibited by both NADH and NAD+ as was growth. The results suggest that plasma membrane electron transport from internal donors to oxygen as an external acceptor is mediated through ECTO-NOX proteins and that electron transport to molecular oxygen may be differentially affected by external pyridine nucleotides depending on cell type.