Cortical spreading depression (CSD) is associated with migraine, stroke, and traumatic brain injury, but its mechanisms remain poorly understood. One of the major features of CSD is an hour-long silencing of neuronal activity. Though this silencing has clear ramifications for CSD-associated disease, it has not been fully explained. We used in vivo whole-cell recordings to examine the effects of CSD on layer 2/3 pyramidal neurons in mouse somatosensory cortex and used in vitro recordings to examine their mechanism. We found that CSD caused a reduction in spontaneous synaptic activity and action potential (AP) firing that lasted over an hour. Both pre- and postsynaptic mechanisms contributed to this silencing. Reductions in frequency of postsynaptic potentials were due to a reduction in presynaptic transmitter release probability as well as reduced AP activity. Decreases in postsynaptic potential amplitude were due to an inhibitory shift in the ratio of excitatory and inhibitory postsynaptic currents. This inhibitory shift in turn contributed to the reduced frequency of APs. Thus, distinct but complementary mechanisms generate the long neuronal silence that follows CSD. These cellular changes could contribute to wider network dysfunction in CSD-associated disease, while the pre- and postsynaptic mechanisms offer separate targets for therapy.

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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.

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 sensori-motor 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 sensori-motor practice period. This hormone exposure accelerated the development of song into stereotyped adult-like 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 sensori-motor phase is not required for their expression.

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 inter-syllable 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.

Recently it was proposed that semiconductor lasers with optical feedback present a regime where they behave as noise driven excitable units. In this work we report on an experimental study in which we periodically force one of these lasers and we compare the results with the solutions of a simple model. The comparison is based on a topological analysis of experimental and theoretical solutions.

Méndez JM, Mindlin GB, Goller F. Interaction between telencephalic signals and respiratory dynamics in songbirds. J Neurophysiol 107: 2971-2983, 2012. First published March 7, 2012 doi:10.1152/jn.00646.2011The 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.

Recently, it was proposed that semiconductor lasers with optical feedback present a complex behavior that can be described as noise driven excitable. In this work we investigate in which region of parameter space this description is adequate. We conclude that the region of the parameter space in which the system displays noise driven excitable behavior is a subset of the region in which presents low frequency fluctuations.