Jorge M. Méndez

Minimum conditions for the induction of cortical spreading depression in brain slices

Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma.

Hormonal acceleration of song development illuminates motor control mechanism in canaries

In songbirds, the ontogeny of singing behavior shows strong parallels with human speech learning. As in humans, development of learned vocal behavior requires exposure to an acoustic model of species‐typical vocalizations, and, subsequently, a sensorimotor practice period after which the vocalization is produced in a stereotyped manner. This requires mastering motor instructions driving the vocal organ and the respiratory system. Recently, it was shown that, in the case of canaries (Serinus canaria), the diverse syllables, constituting the song, are generated with air sac pressure patterns with characteristic shapes, remarkably, those belonging to a very specific mathematical family. Here, we treated juvenile canaries with testosterone at the onset of the sensorimotor practice period. This hormone exposure accelerated the development of song into stereotyped adultlike song. After 20 days of testosterone treatment, subsyringeal air sac pressure patterns of song resembled those produced by adults, while those of untreated control birds of the same age did not. Detailed temporal structure and modulation patterns emerged rapidly with testosterone treatment, and all previously identified categories of adult song were observed. This research shows that the known effect of testosterone on the neural circuits gives rise to the stereotyped categories of respiratory motor gestures. Extensive practice of these motor patterns during the sensorimotor phase is not required for their expression.

Age-related changes in the Bengalese finch song motor program

It is well established that there are remarkable similarities between song learning in oscine birds and acquisition of speech in young children. Human speech shows marked changes with senescence, but few studies have evaluated how song changes with advanced age in songbirds. To investigate the effect of old age on song, we compared song of old Bengalese finches (Lonchura striata domestica) with that of middle-aged birds. The main observed difference was a decrease in the song tempo, largely due to an increased intersyllable duration. Aging also affected the acoustic characteristics of the song, causing a decrease in pitch and in the range of frequency modulations. Gross morphological measurements of selected vocal muscles did not show detectable changes over this age range, suggesting that song deterioration may be due to neural deterioration. The age-induced temporal and acoustic changes in song parallel the acoustic changes that occur in human speech, suggesting songbirds as a suitable model for aging studies on learned vocal behavior.

Interaction between telencephalic signals and respiratory dynamics in songbirds

The mechanisms by which telencephalic areas affect motor activities are largely unknown. They could either take over motor control from downstream motor circuits or interact with the intrinsic dynamics of these circuits. Both models have been proposed for telencephalic control of respiration during learned vocal behavior in birds. The interactive model postulates that simple signals from the telencephalic song control areas are sufficient to drive the nonlinear respiratory network into producing complex temporal sequences. We tested this basic assumption by electrically stimulating telencephalic song control areas and analyzing the resulting respiratory patterns in zebra finches and in canaries. We found strong evidence for interaction between the rhythm of stimulation and the intrinsic respiratory rhythm, including naturally emerging subharmonic behavior and integration of lateralized telencephalic input. The evidence for clear interaction in our experimental paradigm suggests that telencephalic vocal control also uses a similar mechanism. Furthermore, species differences in the response of the respiratory system to stimulation show parallels to differences in the respiratory patterns of song, suggesting that the interactive production of respiratory rhythms is manifested in species-specific specialization of the involved circuitry.

Disrupting vagal feedback affects birdsong motor control.

SUMMARY Coordination of different motor systems for sound production involves the use of feedback mechanisms. Song production in oscines is a well-established animal model for studying learned vocal behavior. Whereas the online use of auditory feedback has been studied in the songbird model, very little is known about the role of other feedback mechanisms. Auditory feedback is required for the maintenance of stereotyped adult song. In addition, the use of somatosensory feedback to maintain pressure during song has been demonstrated with experimentally induced fluctuations in air sac pressure. Feedback information mediating this response is thought to be routed to the central nervous system via afferent fibers of the vagus nerve. Here, we tested the effects of unilateral vagotomy on the peripheral motor patterns of song production and the acoustic features. Unilateral vagotomy caused a variety of disruptions and alterations to the respiratory pattern of song, some of which affected the acoustic structure of vocalizations. These changes were most pronounced a few days after nerve resection and varied between individuals. In the most extreme cases, the motor gestures of respiration were so severely disrupted that individual song syllables or the song motif were atypically terminated. Acoustic changes also suggest altered use of the two sound generators and upper vocal tract filtering, indicating that the disruption of vagal feedback caused changes to the motor program of all motor systems involved in song production and modification. This evidence for the use of vagal feedback by the song system with disruption of song during the first days after nerve cut provides a contrast to the longer-term effects of auditory feedback disruption. It suggests a significant role for somatosensory feedback that differs from that of auditory feedback.

Acquisition of an acoustic template leads to refinement of song motor gestures.

Vocal learning, a key behavior in human speech development, occurs only in a small number of animal taxa. Ontogeny of vocal behavior in humans and songbirds involves acquisition of an acoustic model, which guides the development of self-generated vocalizations (sensorimotor period). How vocal development proceeds in the absence of an acoustic model is largely unknown and cannot be studied directly in humans. Here we explored the effects of an acoustic model on song motor control by comparing peripheral motor gestures (respiration and syringeal muscles) of tutored birds with those of birds raised in acoustic isolation. Although the overall use of syringeal muscles during song was similar in both groups, tutored birds displayed enhanced temporal patterns of activation in respiratory and syringeal motor gestures. Muscle activation was more uniformly distributed throughout the song of tutored birds than that of untutored birds. Similarly, the respiratory effort was similar for both groups, but the expiratory pulses of song contained more modulations and temporal complexity in tutored birds. These results indicate that the acquisition of an acoustic template guides a refinement of experience-independent motor gestures by increasing temporal fine structure, but there is no difference in bilateral activation patterns for a given sound between the two groups. Nevertheless, these subtle temporal changes in muscle activation give rise to pronounced acoustic differences between the songs of the tutored and untutored birds. Experience with song during ontogeny therefore guides a more refined use of experience-independent motor programs.