This article presents a characterization of cortical responses to artificial and natural temporally patterned sounds in the bat species Carollia perspicillata, a species that produces vocalizations at rates above 50 Hz. Multi-unit activity was recorded in three different experiments. In the first experiment, amplitude-modulated (AM) pure tones were used as stimuli to drive auditory cortex (AC) units. AC units of both ketamine-anesthetized and awake bats could lock their spikes to every cycle of the stimulus modulation envelope, but only if the modulation frequency was below 22 Hz. In the second experiment, two identical communication syllables were presented at variable intervals. Suppressed responses to the lagging syllable were observed, unless the second syllable followed the first one with a delay of at least 80 ms (i.e., 12.5 Hz repetition rate). In the third experiment, natural distress vocalization sequences were used as stimuli to drive AC units. Distress sequences produced by C. perspicillata contain bouts of syllables repeated at intervals of ~60 ms (16 Hz). Within each bout, syllables are repeated at intervals as short as 14 ms (~71 Hz). Cortical units could follow the slow temporal modulation flow produced by the occurrence of multisyllabic bouts, but not the fast acoustic flow created by rapid syllable repetition within the bouts. Taken together, our results indicate that even in fast vocalizing animals, such as bats, cortical neurons can only track the temporal structure of acoustic streams modulated at frequencies lower than 22 Hz.

SummaryThe extraction of temporal information from sensory input streams is of paramount importance in the auditory system. In this study, amplitude-modulated sounds were used as stimuli to drive auditory cortex (AC) neurons of the bat species Carollia perspicillata, to assess the interactions between cortical spikes and local-field potentials (LFPs) for the processing of temporal acoustic cues. We observed that neurons in the AC capable of eliciting synchronized spiking to periodic acoustic envelopes were significantly more coherent to theta- and alpha-band LFPs than their non-synchronized counterparts. These differences occurred independently of the modulation rate tested and could not be explained by power or phase modulations of the field potentials. We argue that the coupling between neuronal spiking and the phase of low-frequency LFPs might be important for orchestrating the coding of temporal acoustic structures in the AC.

The stimulation of the AMP-activated kinase (AMPK) by 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) has been associated with antihyperalgesia and the inhibition of nociceptive signaling in the spinal cord in models of paw inflammation. The attenuated nociception comes along with a strongly reduced paw edema, indicating that peripheral antiinflammatory mechanisms contribute to antinociception. In this study, we investigated the impact of AICAR on the immune cell composition in inflamed paws, as well as the regulation of inflammatory and resolving markers in macrophages. By using fluorescence-activated cell sorting (FACS) analysis and immunofluorescence, we found a significantly increased fraction of proresolving M2 macrophages and anti-inflammatory interleukin (IL)-10 in inflamed tissue, while M1 macrophages and proinflammatory cytokines such as IL-1 were decreased by AICAR in wild type mice. In AMPKα2 knock-out mice, the M2 polarization of macrophages in the paw was missing. The results were supported by experiments in primary macrophage cultures which also showed a shift to a proresolving phenotype with decreased levels of proinflammatory mediators and increased levels of antiinflammatory mediators. However, in the cell cultures, we did not observe differences between the AMPKα2+/+ and −/− cells, thus indicating that the AICAR-induced effects are at least partially AMPK-independent. In summary, our results indicate that AICAR has potent antiinflammatory and proresolving properties in inflammation which are contributing to a reduction of inflammatory edema and antinociception.

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