A feedforward inhibitory premotor circuit for auditory-vocal interactions in zebra finches.

During vocal exchanges, hearing specific auditory signals can provoke vocal responses or suppress vocalizations to avoid interference. These abilities result in the widespread phenomenon of vocal turn taking, yet little is known about the neural circuitry that regulates the input-dependent timing of vocal replies. Previous work in vocally interacting zebra finches has highlighted the importance of premotor inhibition for precisely timed vocal output. By developing physiologically constrained mathematical models, we derived circuit mechanisms based on feedforward inhibition that enable both the temporal modulation of vocal premotor drive as well as auditory suppression of vocalization during listening. Extracellular recordings in HVC during the listening phase confirmed the presence of auditory-evoked response patterns in putative inhibitory interneurons, along with corresponding signatures of auditory-evoked activity suppression. Further, intracellular recordings of identified neurons projecting to HVC from the upstream sensorimotor nucleus, nucleus interfacialis (NIf), shed light on the timing of auditory inputs to this network. The analysis of incrementally time-lagged interactions between auditory and premotor activity in the model resulted in the prediction of a window of auditory suppression, which could be, in turn, verified in behavioral data. A phasic feedforward inhibition model consistently explained the experimental results. This mechanism highlights a parsimonious and generalizable principle for how different driving inputs (vocal and auditory related) can be integrated in a single sensorimotor circuit to regulate two opposing vocal behavioral outcomes: the controlled timing of vocal output or the suppression of overlapping vocalizations.

Neural optimization: Understanding trade-offs with Pareto theory.

Nervous systems, like any organismal structure, have been shaped by evolutionary processes to increase fitness. The resulting neural 'bauplan' has to account for multiple objectives simultaneously, including computational function, as well as additional factors such as robustness to environmental changes and energetic limitations. Oftentimes these objectives compete, and quantification of the relative impact of individual optimization targets is non-trivial. Pareto optimality offers a theoretical framework to decipher objectives and trade-offs between them. We, therefore, highlight Pareto theory as a useful tool for the analysis of neurobiological systems from biophysically detailed cells to large-scale network structures and behavior. The Pareto approach can help to assess optimality, identify relevant objectives and their respective impact, and formulate testable hypotheses.

Differential Song Deficits after Lentivirus-Mediated Knockdown of FoxP1, FoxP2, or FoxP4 in Area X of Juvenile Zebra Finches.

Mutations in the transcription factors FOXP1 and FOXP2 are associated with speech impairments. FOXP1 is additionally linked to cognitive deficits, as is FOXP4. These FoxP proteins are highly conserved in vertebrates and expressed in comparable brain regions, including the striatum. In male zebra finches, experimental manipulation of FoxP2 in Area X, a striatal song nucleus essential for vocal production learning, affects song development, adult song production, dendritic spine density, and dopamine-regulated synaptic transmission of striatal neurons. We previously showed that, in the majority of Area X neurons FoxP1, FoxP2, and FoxP4 are coexpressed, can dimerize and multimerize with each other and differentially regulate the expression of target genes. These findings raise the possibility that FoxP1, FoxP2, and FoxP4 (FoxP1/2/4) affect neural function differently and in turn vocal learning. To address this directly, we downregulated FoxP1 or FoxP4 in Area X of juvenile zebra finches and compared the resulting song phenotypes with the previously described inaccurate and incomplete song learning after FoxP2 knockdown. We found that experimental downregulation of FoxP1 and FoxP4 led to impaired song learning with partly similar features as those reported for FoxP2 knockdowns. However, there were also specific differences between the groups, leading us to suggest that specific features of the song are differentially impacted by developmental manipulations of FoxP1/2/4 expression in Area X.SIGNIFICANCE STATEMENT We compared the effects of experimentally reduced expression of the transcription factors FoxP1, FoxP2, and FoxP4 in a striatal song nucleus, Area X, on vocal production learning in juvenile male zebra finches. We show, for the first time, that these temporally and spatially precise manipulations of the three FoxPs affect spectral and temporal song features differentially. This is important because it raises the possibility that the different FoxPs control different aspects of vocal learning through combinatorial gene expression or by acting in different microcircuits within Area X. These results are consistent with the deleterious effects of human FOXP1 and FOXP2 mutations on speech and language and add FOXP4 as a possible candidate gene for vocal disorders.

General isochronous rhythm in echolocation calls and social vocalizations of the bat Saccopteryx bilineata.

Rhythm is an essential component of human speech and music but very little is known about its evolutionary origin and its distribution in animal vocalizations. We found a regular rhythm in three multisyllabic vocalization types (echolocation call sequences, male territorial songs and pup isolation calls) of the neotropical bat Saccopteryx bilineata. The intervals between element onsets were used to fit the rhythm for each individual. For echolocation call sequences, we expected rhythm frequencies around 6-24 Hz, corresponding to the wingbeat in S. bilineata which is strongly coupled to echolocation calls during flight. Surprisingly, we found rhythm frequencies between 6 and 24 Hz not only for echolocation sequences but also for social vocalizations, e.g. male territorial songs and pup isolation calls, which were emitted while bats were stationary. Fourier analysis of element onsets confirmed an isochronous rhythm across individuals and vocalization types. We speculate that attentional tuning to the rhythms of echolocation calls on the receivers' side might make the production of equally steady rhythmic social vocalizations beneficial.

Honeybees Learn Landscape Features during Exploratory Orientation Flights.

Exploration is an elementary and fundamental form of learning about the structure of the world [1-3]. Little is known about what exactly is learned when an animal seeks to become familiar with the environment. Navigating animals explore the environment for safe return to an important place (e.g., a nest site) and to travel between places [4]. Flying central-place foragers like honeybees (Apis mellifera) extend their exploration into distances from which the features of the nest cannot be directly perceived [5-10]. Bees perform short-range and long-range orientations flights. Short-range flights are performed in the immediate surroundings of the hive and occur more frequently under unfavorable weather conditions, whereas long-range flights lead the bees into different sectors of the surrounding environment [11]. Applying harmonic radar technology for flight tracking, we address the question of whether bees learn landscape features during their first short-range or long-range orientation flight. The homing flights of single bees were compared after they were displaced to areas explored or not explored during the orientation flight. Bees learn the landscape features during the first orientation flight since they returned faster and along straighter flights from explored areas as compared to unexplored areas. We excluded a range of possible factors that might have guided bees back to the hive based on egocentric navigation strategies (path integration, beacon orientation, and pattern matching of the skyline). We conclude that bees localize themselves according to learned ground structures and their spatial relations to the hive.

"Bird Song Metronomics": Isochronous Organization of Zebra Finch Song Rhythm.

The human capacity for speech and vocal music depends on vocal imitation. Songbirds, in contrast to non-human primates, share this vocal production learning with humans. The process through which birds and humans learn many of their vocalizations as well as the underlying neural system exhibit a number of striking parallels and have been widely researched. In contrast, rhythm, a key feature of language, and music, has received surprisingly little attention in songbirds. Investigating temporal periodicity in bird song has the potential to inform the relationship between neural mechanisms and behavioral output and can also provide insight into the biology and evolution of musicality. Here we present a method to analyze birdsong for an underlying rhythmic regularity. Using the intervals from one note onset to the next as input, we found for each bird an isochronous sequence of time stamps, a "signal-derived pulse," or pulse(S), of which a subset aligned with all note onsets of the bird's song. Fourier analysis corroborated these results. To determine whether this finding was just a byproduct of the duration of notes and intervals typical for zebra finches but not dependent on the individual duration of elements and the sequence in which they are sung, we compared natural songs to models of artificial songs. Note onsets of natural song deviated from the pulse(S) significantly less than those of artificial songs with randomized note and gap durations. Thus, male zebra finch song has the regularity required for a listener to extract a perceived pulse (pulse(P)), as yet untested. Strikingly, in our study, pulses(S) that best fit note onsets often also coincided with the transitions between sub-note elements within complex notes, corresponding to neuromuscular gestures. Gesture durations often equaled one or more pulse(S) periods. This suggests that gesture duration constitutes the basic element of the temporal hierarchy of zebra finch song rhythm, an interesting parallel to the hierarchically structured components of regular rhythms in human music.

A common frame of reference for learned and communicated vectors in honeybee navigation.

Humans draw maps when communicating about places or verbally describe routes between locations. Honeybees communicate places by encoding distance and direction in their waggle dances. Controversy exists not only about the structure of spatial memory but also about the efficiency of dance communication. Some of these uncertainties were resolved by studies in which recruits' flights were monitored using harmonic radar. We asked whether the two sources of vector information--the previously learned flight vector to a food source and the communicated vector--are represented in a common frame of spatial reference. We found that recruits redirect their outbound flights and perform novel shortcut flights between the communicated and learned locations in both directions. Guidance by beacons at the respective locations or by the panorama of the horizon was excluded. These findings indicate a spatial reference based on either large-scale vector integration or a common geocentric map-like spatial memory. Both models predict a memory structure that stores the spatial layout in such a way that decisions are made according to estimated distances and directions. The models differ with respect to the role of landmarks and the time of learning of spatial relations.