@article{pang_baker_murthy_pillow_2024, title={Inferring neural dynamics of memory during naturalistic social communication}, url={https://doi.org/10.1101/2024.01.26.577404}, DOI={10.1101/2024.01.26.577404}, abstractNote={Memory processes in complex behaviors like social communication require forming representations of the past that grow with time. The neural mechanisms that support such continually growing memory remain unknown. We address this gap in the context of fly courtship, a natural social behavior involving the production and perception of long, complex song sequences. To study female memory for male song history in unrestrained courtship, we present ‘Natural Continuation’ (NC)—a general, simulation-based model comparison procedure to evaluate candidate neural codes for complex stimuli using naturalistic behavioral data. Applying NC to fly courtship revealed strong evidence for an adaptive population mechanism for how female auditory neural dynamics could convert long song histories into a rich mnemonic format. Song temporal patterning is continually transformed by heterogeneous nonlinear adaptation dynamics, then integrated into persistent activity, enabling common neural mechanisms to retain continuously unfolding information over long periods and yielding state-of-the-art predictions of female courtship behavior. At a population level this coding model produces multi-dimensional advection-diffusion-like responses that separate songs over a continuum of timescales and can be linearly transformed into flexible output signals, illustrating its potential to create a generic, scalable mnemonic format for extended input signals poised to drive complex behavioral responses. This work thus shows how naturalistic behavior can directly inform neural population coding models, revealing here a novel process for memory formation.}, author={Pang, Rich and Baker, Christa and Murthy, Mala and Pillow, Jonathan}, year={2024}, month={Jan} }
@article{baker_guan_choi_murthy_2024, title={The role of fruitless in specifying courtship behaviors across divergent Drosophila species}, volume={10}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.adk1273}, DOI={10.1126/sciadv.adk1273}, abstractNote={
Sex-specific behaviors are critical for reproduction and species survival. The sex-specifically spliced transcription factor
fruitless
(
fru
) helps establish male courtship behaviors in invertebrates. Forcing male-specific
fru
(
fruM
) splicing in
Drosophila melanogaster
females produces male-typical behaviors while disrupting female-specific behaviors. However, whether
fru
’s joint role in specifying male and inhibiting female behaviors is conserved across species is unknown. We used CRISPR-Cas9 to force FruM expression in female
Drosophila virilis
, a species in which males and females produce sex-specific songs
.
In contrast to
D. melanogaster
, in which one
fruM
allele is sufficient to generate male behaviors in females, two alleles are needed in
D. virilis
females.
D. virilis
females expressing FruM maintain the ability to sing female-typical song as well as lay eggs, whereas
D. melanogaster
FruM females cannot lay eggs. These results reveal potential differences in
fru
function between divergent species and underscore the importance of studying diverse behaviors and species for understanding the genetic basis of sex differences.
}, number={11}, journal={SCIENCE ADVANCES}, author={Baker, Christa A. and Guan, Xiao-Juan and Choi, Minseung and Murthy, Mala}, year={2024}, month={Mar} }
@article{baker_guan_choi_murthy_2023, title={The role offruitlessin specifying courtship behaviors differs acrossDrosophilaspecies}, url={https://doi.org/10.1101/2023.09.01.556001}, DOI={10.1101/2023.09.01.556001}, abstractNote={AbstractSex-specific behaviors are critical for reproduction and species survival. The sex-specifically spliced transcription factorfruitless(fru) helps establish male courtship behaviors in invertebrates. Forcing male-specificfru(fruM) splicing inDrosophila melanogasterfemales produces male-typical behaviors, while disrupting female-specific behaviors. However, whetherfru’s joint role in specifying male and inhibiting female behaviors is conserved across species is unknown. We used CRISPR/Cas9 to force FruM expression in femaleD. virilis, a species in which males and females produce sex-specific songs. In contrast toD. melanogaster, in which onefruMallele is sufficient to generate male behaviors in females, two alleles are needed inD. virilisfemales.D. virilisfemales expressing FruM maintain the ability to sing female-typical song as well as lay eggs, whereasD. melanogasterFruM females cannot lay eggs. These results reveal important differences infrufunction between divergent species and underscore the importance of studying diverse behaviors and species for understanding the genetic basis of sex differences.}, author={Baker, Christa A. and Guan, Xiao-Juan and Choi, Minseung and Murthy, Mala}, year={2023}, month={Sep} }
@article{baker_mckellar_pang_nern_dorkenwald_pacheco_eckstein_funke_dickson_murthy_2022, title={Neural network organization for courtship-song feature detection in Drosophila}, url={http://dx.doi.org/10.1016/j.cub.2022.06.019}, DOI={10.1016/j.cub.2022.06.019}, abstractNote={Animals communicate using sounds in a wide range of contexts, and auditory systems must encode behaviorally relevant acoustic features to drive appropriate reactions. How feature detection emerges along auditory pathways has been difficult to solve due to challenges in mapping the underlying circuits and characterizing responses to behaviorally relevant features. Here, we study auditory activity in the Drosophila melanogaster brain and investigate feature selectivity for the two main modes of fly courtship song, sinusoids and pulse trains. We identify 24 new cell types of the intermediate layers of the auditory pathway, and using a new connectomic resource, FlyWire, we map all synaptic connections between these cell types, in addition to connections to known early and higher-order auditory neurons-this represents the first circuit-level map of the auditory pathway. We additionally determine the sign (excitatory or inhibitory) of most synapses in this auditory connectome. We find that auditory neurons display a continuum of preferences for courtship song modes and that neurons with different song-mode preferences and response timescales are highly interconnected in a network that lacks hierarchical structure. Nonetheless, we find that the response properties of individual cell types within the connectome are predictable from their inputs. Our study thus provides new insights into the organization of auditory coding within the Drosophila brain.}, journal={Current Biology}, author={Baker, Christa A. and McKellar, Claire and Pang, Rich and Nern, Aljoscha and Dorkenwald, Sven and Pacheco, Diego A. and Eckstein, Nils and Funke, Jan and Dickson, Barry J. and Murthy, Mala}, year={2022}, month={Aug} }
@article{dorkenwald_mckellar_macrina_kemnitz_lee_lu_wu_popovych_mitchell_nehoran_et al._2022, title={FlyWire: online community for whole-brain connectomics}, url={http://dx.doi.org/10.1038/s41592-021-01330-0}, DOI={10.1038/s41592-021-01330-0}, abstractNote={Due to advances in automated image acquisition and analysis, whole-brain connectomes with 100,000 or more neurons are on the horizon. Proofreading of whole-brain automated reconstructions will require many person-years of effort, due to the huge volumes of data involved. Here we present FlyWire, an online community for proofreading neural circuits in a Drosophila melanogaster brain and explain how its computational and social structures are organized to scale up to whole-brain connectomics. Browser-based three-dimensional interactive segmentation by collaborative editing of a spatially chunked supervoxel graph makes it possible to distribute proofreading to individuals located virtually anywhere in the world. Information in the edit history is programmatically accessible for a variety of uses such as estimating proofreading accuracy or building incentive systems. An open community accelerates proofreading by recruiting more participants and accelerates scientific discovery by requiring information sharing. We demonstrate how FlyWire enables circuit analysis by reconstructing and analyzing the connectome of mechanosensory neurons. FlyWire is an online community and a platform for proofreading electron microscopy-based connectome data of the Drosophila brain.}, journal={Nature Methods}, author={Dorkenwald, Sven and McKellar, Claire E. and Macrina, Thomas and Kemnitz, Nico and Lee, Kisuk and Lu, Ran and Wu, Jingpeng and Popovych, Sergiy and Mitchell, Eric and Nehoran, Barak and et al.}, year={2022}, month={Jan} }
@article{baker_mckellar_nern_dorkenwald_pacheco_pang_eckstein_funke_dickson_murthy_2020, title={Neural Network Organization for Courtship Song Feature Detection inDrosophila}, url={https://doi.org/10.1101/2020.10.08.332148}, DOI={10.1101/2020.10.08.332148}, abstractNote={ABSTRACTAnimals communicate using sounds in a wide range of contexts, and auditory systems must encode behaviorally relevant acoustic features to drive appropriate reactions. How feature detection emerges along auditory pathways has been difficult to solve due to challenges in mapping the underlying circuits and characterizing responses to behaviorally relevant features. Here, we study auditory activity in theDrosophila melanogasterbrain and investigate feature selectivity for the two main modes of fly courtship song, sinusoids and pulse trains. We identify 24 new cell types of the intermediate layers of the auditory pathway, and using a new connectomic resource, FlyWire, we map all synaptic connections between these cell types, in addition to connections to known early and higher-order auditory neurons - this represents the first map of the auditory pathway. We additionally determine the sign (excitatory or inhibitory) of most synapses in this auditory connectome. We find that auditory neurons display a continuum of preferences for courtship song modes, and that neurons with different song mode preferences are highly interconnected in a network that lacks hierarchical structure. Among this network, frequency tuning is centered on the range of frequencies present in song, whereas pulse rate tuning extends to rates outside of song, suggesting that these neurons form a basis set for downstream processing. Our study provides new insights into the organization of auditory coding within theDrosophilabrain.}, author={Baker, Christa A. and McKellar, Claire and Nern, Aljoscha and Dorkenwald, Sven and Pacheco, Diego A. and Pang, Rich and Eckstein, Nils and Funke, Jan and Dickson, Barry J. and Murthy, Mala}, year={2020}, month={Oct} }
@article{baker_clemens_murthy_2019, title={Acoustic Pattern Recognition and Courtship Songs: Insights from Insects}, url={http://dx.doi.org/10.1146/annurev-neuro-080317-061839}, DOI={10.1146/annurev-neuro-080317-061839}, abstractNote={Across the animal kingdom, social interactions rely on sound production and perception. From simple cricket chirps to more elaborate bird songs, animals go to great lengths to communicate information critical for reproduction and survival via acoustic signals. Insects produce a wide array of songs to attract a mate, and the intended receivers must differentiate these calls from competing sounds, analyze the quality of the sender from spectrotemporal signal properties, and then determine how to react. Insects use numerically simple nervous systems to analyze and respond to courtship songs, making them ideal model systems for uncovering the neural mechanisms underlying acoustic pattern recognition. We highlight here how the combination of behavioral studies and neural recordings in three groups of insects—crickets, grasshoppers, and fruit flies—reveals common strategies for extracting ethologically relevant information from acoustic patterns and how these findings might translate to other systems.}, journal={Annual Review of Neuroscience}, author={Baker, Christa A. and Clemens, Jan and Murthy, Mala}, year={2019}, month={Jul} }
@article{baker_ma_casareale_carlson_2016, title={Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals}, url={https://doi.org/10.1523/JNEUROSCI.0648-16.2016}, DOI={10.1523/JNEUROSCI.0648-16.2016}, abstractNote={In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ∼8–12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. SIGNIFICANCE STATEMENT The timing patterns of action potentials, or spikes, play important roles in representing information in the nervous system. However, how these temporal patterns are recognized by downstream neurons is not well understood. Here we use the electrosensory system of mormyrid weakly electric fish to investigate how a population of neurons with diverse temporal filtering properties encodes behaviorally relevant input timing patterns, and how this relates to behavioral sensitivity. We show that fish are behaviorally sensitive to millisecond variations in natural, temporally patterned communication signals, and that the responses of individual midbrain neurons are also sensitive to variation in these patterns. In fact, the output of single neurons contains enough information to discriminate stereotyped communication signals produced by different individuals.}, journal={The Journal of Neuroscience}, author={Baker, Christa A. and Ma, Lisa and Casareale, Chelsea R. and Carlson, Bruce A.}, year={2016}, month={Aug} }
@article{baker_huck_carlson_2015, title={Peripheral sensory coding through oscillatory synchrony in weakly electric fish}, volume={4}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84941287137&partnerID=MN8TOARS}, DOI={10.7554/eLife.08163}, abstractNote={Adaptations to an organism's environment often involve sensory system modifications. In this study, we address how evolutionary divergence in sensory perception relates to the physiological coding of stimuli. Mormyrid fishes that can detect subtle variations in electric communication signals encode signal waveform into spike-timing differences between sensory receptors. In contrast, the receptors of species insensitive to waveform variation produce spontaneously oscillating potentials. We found that oscillating receptors respond to electric pulses by resetting their phase, resulting in transient synchrony among receptors that encodes signal timing and location, but not waveform. These receptors were most sensitive to frequencies found only in the collective signals of groups of conspecifics, and this was correlated with increased behavioral responses to these frequencies. Thus, different perceptual capabilities correspond to different receptor physiologies. We hypothesize that these divergent mechanisms represent adaptations for different social environments. Our findings provide the first evidence for sensory coding through oscillatory synchrony.}, number={AUGUST2015}, journal={eLife}, author={Baker, C.A. and Huck, K.R. and Carlson, B.A.}, year={2015} }
@article{baker_carlson_2014, title={Short-term depression, temporal summation, and onset inhibition shape interval tuning in midbrain neurons}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84908062304&partnerID=MN8TOARS}, DOI={10.1523/JNEUROSCI.2299-14.2014}, abstractNote={A variety of synaptic mechanisms can contribute to single-neuron selectivity for temporal intervals in sensory stimuli. However, it remains unknown how these mechanisms interact to establish single-neuron sensitivity to temporal patterns of sensory stimulationin vivo. Here we address this question in a circuit that allows us to control the precise temporal patterns of synaptic input to interval-tuned neurons in behaviorally relevant ways. We obtainedin vivointracellular recordings under multiple levels of current clamp from midbrain neurons in the mormyrid weakly electric fishBrienomyrus brachyistiusduring stimulation with electrosensory pulse trains. To reveal the excitatory and inhibitory inputs onto interval-tuned neurons, we then estimated the synaptic conductances underlying responses. We found short-term depression in excitatory and inhibitory pathways onto all interval-tuned neurons. Short-interval selectivity was associated with excitation that depressed less than inhibition at short intervals, as well as temporally summating excitation. Long-interval selectivity was associated with long-lasting onset inhibition. We investigated tuning after separately nullifying the contributions of temporal summation and depression, and found the greatest diversity of interval selectivity among neurons when both mechanisms were at play. Furthermore, eliminating the effects of depression decreased sensitivity to directional changes in interval. These findings demonstrate that variation in depression and summation of excitation and inhibition helps to establish tuning to behaviorally relevant intervals in communication signals, and that depression contributes to neural coding of interval sequences. This work reveals for the first time how the interplay between short-term plasticity and temporal summation mediates the decoding of temporal sequences in awake, behaving animals.}, number={43}, journal={Journal of Neuroscience}, author={Baker, C.A. and Carlson, B.A.}, year={2014}, pages={14272–14287} }
@article{baker_kohashi_lyons-warren_ma_carlson_2013, title={Multiplexed temporal coding of electric communication signals in mormyrid fishes}, volume={216}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879528408&partnerID=MN8TOARS}, DOI={10.1242/jeb.082289}, abstractNote={SummaryThe coding of stimulus information into patterns of spike times occurs widely in sensory systems. Determining how temporally coded information is decoded by central neurons is essential to understanding how brains process sensory stimuli. Mormyrid weakly electric fishes are experts at time coding, making them an exemplary organism for addressing this question. Mormyrids generate brief, stereotyped electric pulses. Pulse waveform carries information about sender identity, and it is encoded into submillisecond-to-millisecond differences in spike timing between receptors. Mormyrids vary the time between pulses to communicate behavioral state, and these intervals are encoded into the sequence of interspike intervals within receptors. Thus, the responses of peripheral electroreceptors establish a temporally multiplexed code for communication signals, one consisting of spike timing differences between receptors and a second consisting of interspike intervals within receptors. These signals are processed in a dedicated sensory pathway, and recent studies have shed light on the mechanisms by which central circuits can extract behaviorally relevant information from multiplexed temporal codes. Evolutionary change in the anatomy of this pathway is related to differences in electrosensory perception, which appears to have influenced the diversification of electric signals and species. However, it remains unknown how this evolutionary change relates to differences in sensory coding schemes, neuronal circuitry and central sensory processing. The mormyrid electric communication pathway is a powerful model for integrating mechanistic studies of temporal coding with evolutionary studies of correlated differences in brain and behavior to investigate neural mechanisms for processing temporal codes.}, number={13}, journal={Journal of Experimental Biology}, author={Baker, C.A. and Kohashi, T. and Lyons-Warren, A.M. and Ma, X. and Carlson, B.A.}, year={2013}, pages={2365–2379} }
@article{o’neil_limb_baker_ryugo_2010, title={Bilateral effects of unilateral cochlear implantation in congenitally deaf cats}, volume={518}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77952144378&partnerID=MN8TOARS}, DOI={10.1002/cne.22339}, abstractNote={AbstractCongenital deafness results in synaptic abnormalities in auditory nerve endings. These abnormalities are most prominent in terminals called endbulbs of Held, which are large, axosomatic synaptic endings whose size and evolutionary conservation emphasize their importance. Transmission jitter, delay, or failures, which would corrupt the processing of timing information, are possible consequences of the perturbations at this synaptic junction. We sought to determine whether electrical stimulation of the congenitally deaf auditory system via cochlear implants would restore the endbulb synapses to their normal morphology. Three and 6‐month‐old congenitally deaf cats received unilateral cochlear implants and were stimulated for a period of 10–19 weeks by using human speech processors. Implanted cats exhibited acoustic startle responses and were trained to approach their food dish in response to a specific acoustic stimulus. Endbulb synapses were examined by using serial section electron microscopy from cohorts of cats with normal hearing, congenital deafness, or congenital deafness with a cochlear implant. Synapse restoration was evident in endbulb synapses on the stimulated side of cats implanted at 3 months of age but not at 6 months. In the young implanted cats, postsynaptic densities exhibited normal size, shape, and distribution, and synaptic vesicles had density values typical of hearing cats. Synapses of the contralateral auditory nerve in early implanted cats also exhibited synapses with more normal structural features. These results demonstrate that electrical stimulation with a cochlear implant can help preserve central auditory synapses through direct and indirect pathways in an age‐dependent fashion. J. Comp. Neurol. 518:2382–2404, 2010. © 2010 Wiley‐Liss, Inc.}, number={12}, journal={Journal of Comparative Neurology}, author={O’Neil, J.N. and Limb, C.J. and Baker, C.A. and Ryugo, D.K.}, year={2010}, pages={2382–2404} }
@article{o’neil_limb_baker_ryugo_2010, title={Erratum: Bilateral effects of unilateral cochlear implantation in congenitally deaf cats (The Journal of Comparative Neurology (2010) 518 (2382-2404))}, volume={518}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77955697779&partnerID=MN8TOARS}, DOI={10.1002/cne.22473}, abstractNote={In our recently published paper, we inadvertently listed the statistical test used for our analysis p 2387 as Tukey-Hansen HDS. The correct test is Tukey-Kramer HSD. The authors sincerely regret this error and any inconvenience it may have caused.}, number={19}, journal={Journal of Comparative Neurology}, author={O’Neil, J.N. and Limb, C.J. and Baker, C.A. and Ryugo, D.K.}, year={2010} }
@article{baker_montey_pongstaporn_ryugo_2010, title={Postnatal development of the endbulb of held in congenitally deaf cats}, volume={4}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77953389373&partnerID=MN8TOARS}, DOI={10.3389/fnana.2010.00019}, abstractNote={The endbulbs of Held are formed by the ascending branches of myelinated auditory nerve fibers and represent one of the largest synaptic endings in the brain. Normally, these endings are highly branched and each can form up to 1000 dome-shaped synapses. The deaf white cat is a model of congenital deafness involving a type of cochleosaccular degeneration that mimics the Scheibe deformity in humans. Endbulbs of mature deaf white cats exhibit reduced branching, hypertrophy of postsynaptic densities (PSDs), and changes in synaptic vesicle density. Because cats are essentially deaf at birth, we sought to determine if the progression of brain abnormalities was linked in time to the failure of normal hearing development. The rationale was that the lack of sound-evoked activity would trigger pathologic change in deaf kittens. The cochleae of deaf cats did not exhibit abnormal morphology at birth. After the first postnatal week, however, the presence of a collapsed scala media signaled the difference between deaf and hearing cats. By working backwards in age, endbulbs of deaf cats expressed flattened and elongated PSDs and increased synaptic vesicle density as compared to normal endbulbs. These differences are present at birth in some white kittens, presaging deafness despite their normal cochlear histology. We speculate that hearing pathology is signaled by a perinatal loss of spontaneous bursting activity in auditory nerve fibers or perhaps by some factor released by hair cell synapses before obliteration of the organ of Corti.}, journal={Frontiers in Neuroanatomy}, author={Baker, C.A. and Montey, K.L. and Pongstaporn, T. and Ryugo, D.K.}, year={2010} }
@article{ryugo_baker_montey_chang_coco_fallon_shepherd_2010, title={Synaptic plasticity after chemical deafening and electrical stimulation of the auditory nerve in cats}, volume={518}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77949354102&partnerID=MN8TOARS}, DOI={10.1002/cne.22262}, abstractNote={AbstractThe effects of deafness on brain structure and function have been studied using animal models of congenital deafness that include surgical ablation of the organ of Corti, acoustic trauma, ototoxic drugs, and hereditary deafness. This report describes the morphologic plasticity of auditory nerve synapses in response to ototoxic deafening and chronic electrical stimulation of the auditory nerve. Normal kittens were deafened by neonatal administration of neomycin that eliminated auditory receptor cells. Some of these cats were raised deaf, whereas others were chronically implanted with cochlear electrodes at 2 months of age and electrically stimulated for up to 12 months. The large endings of the auditory nerve, endbulbs of Held, were studied because they hold a key position in the timing pathway for sound localization, are readily identifiable, and exhibit deafness‐associated abnormalities. Compared with those of normal hearing cats, synapses of ototoxically deafened cats displayed expanded postsynaptic densities, a 35.4% decrease in synaptic vesicle (SV) density, and a reduction in the somatic size of spherical bushy cells (SBCs). In comparison with normal hearing cats, ototoxically deafened cats that received cochlear stimulation had endbulbs that expressed postsynaptic densities (PSDs) that were statistically identical in size, showed a 48.1% reduction in SV density, and whose target SBCs had a 25.5% reduction in soma area. These results demonstrate that electrical stimulation via a cochlear implant in chemically deafened cats preserves PSD size but not other aspects of synapse morphology. This determination further suggests that the effects of ototoxic deafness are not identical to those of hereditary deafness. J. Comp. Neurol. 518:1046–1063, 2010. © 2009 Wiley‐Liss, Inc.}, number={7}, journal={Journal of Comparative Neurology}, author={Ryugo, D.K. and Baker, C.A. and Montey, K.L. and Chang, L.Y. and Coco, A. and Fallon, J.B. and Shepherd, R.K.}, year={2010}, pages={1046–1063} }