Biology subjects

Dougherty, K.

Publications and source records attributed to Dougherty, K..

10 recordsLinked to original sources

bioRxiv2025

Causal role for pulvinar burst firing in thalamo-cortical attention control

The primate pulvinar has been implicated in coordinating cortical networks during attention, but its causal role remains elusive. Like other thalamic nuclei, pulvinar neurons switch between tonic and burst firing, but whether bursts influence behavior and cognitive processes is unknown. Here, we show that pulvinar bursts are not only modulated by attention but also predict behavioral performance. In macaques performing a covert attention task, bursts were more frequent for non-cued targets and uniquely reconfigured population codes in parietal cortex. Crucially, electrical microstimulation of pulvinar triggered bursts that enhanced target detection and synchronized cortical spiking, with behavioral benefits scaling with the strength of burst recruitment. These results establish pulvinar bursts as a causal driver of attention, revealing a thalamo-cortical mechanism by which thalamus exerts moment-to-moment control over cortical processing and behavior.

animal behavior and cognition↗

bioRxiv2024

Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury

Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individuals outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-kB dependent in VGluT2+ INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.

neuroscience↗

bioRxiv2023

Near-field potentials index local neural computations more accurately than population spiking

Local field potentials (LFP) are low-frequency extracellular voltage fluctuations thought to primarily arise from synaptic activity. However, unlike highly localized neuronal spiking, LFP is spatially less specific. LFP measured at one location is not entirely generated there due to far-field contributions that are passively conducted across volumes of neural tissue. We sought to quantify how much information within the locally generated, near-field low-frequency activity (nfLFP) is masked by volume-conducted far-field signals. To do so, we measured laminar neural activity in primary visual cortex (V1) of monkeys viewing sequences of multifeatured stimuli. We compared information content of regular LFP and nfLFP that was mathematically stripped of volume-conducted far-field contributions. Information content was estimated by decoding stimulus properties from neural responses via spatiotemporal multivariate pattern analysis. Volume-conducted information differed from locally generated information in two important ways: (1) for stimulus features relevant to V1 processing (orientation and eye-of-origin), nfLFP contained more information. (2) in contrast, the volume-conducted signal was more informative regarding temporal context (relative stimulus position in a sequence), a signal likely to be coming from elsewhere. Moreover, LFP and nfLFP differed both spectrally as well as spatially, urging caution regarding the interpretations of individual frequency bands and/or laminar patterns of LFP. Most importantly, we found that population spiking of local neurons was less informative than either the LFP or nfLFP, with nfLFP containing most of the relevant information regarding local stimulus processing. These findings suggest that the optimal way to read out local computational processing from neural activity is to decode the local contributions to LFP, with significant information loss hampering both regular LFP and local spiking. Authors ContributionsConceptualization, D.A.T., J.A.W, and A.M.; Data Collection, J.A.W., M.A.C., K.D.; Formal Analysis, D.A.T. and J.A.W.; Data Visualization, D.A.T. and J.A.W.; Original Draft, D.A.T., J.A.W., and A.M.; Revisions and Final Draft, D.A.T., J.A.W., M.A.C., K.D., M.T.W., A.M.B., and A.M. Competing InterestsThe authors declare no conflicts of interest.

neuroscience↗

bioRxiv2022

Reversible edema following electric drilling of macaque craniotomy

In-vivo electrophysiology requires direct access to brain tissue, necessitating the development and refinement of surgical procedures and techniques that promote the health and well-being of the animal subjects. Here, we report a series of findings noted on structural magnetic resonance imaging (MRI) scans in monkeys with MRI-compatible implants following small craniotomies that provide access for intracranial electrophysiology. We found distinct brain regions exhibiting hyperintensities in T2-weighted scans that were prominent underneath the sites at which craniotomies had been performed. We interpreted these hyperintensities as edema of the neural tissue and found that they were predominantly present following electric drilling, but not when manual, hand-operated drills were used. Further, the anomalies subsided within 2-3 weeks following surgery. Our report highlights the utility of MRI-compatible implants that promote clinical examination of the animals brain, sometimes revealing findings that may go unnoticed when incompatible implants are used. We show replicable differences in outcome when using electric vs. mechanical devices, both ubiquitous in the field. If electric drills are used, our report cautions electrophysiological recordings from tissue directly underneath the craniotomy for the first 2-3 weeks following the procedure due to putative edema.

neuroscience↗

bioRxiv2021

Does extracellular DNA mask microbial responses to a pulse disturbance?

A major goal in microbial ecology is to predict how microbial communities will respond to global change. However, DNA-based sequencing that is intended to characterize live microbial communities includes extracellular DNA (exDNA) from non-viable cells. This could obscure relevant microbial responses, particularly to pulse disturbances which kill bacteria and have disproportionate effects on ecosystems. Here, we characterize bacterial communities before and after a drying-rewetting pulse disturbance, using an improved method for exDNA exclusion. We find that exDNA removal is important for detecting subtle yet significant changes in microbial abundance, diversity, and community composition across the disturbance. However, inclusion of exDNA did not obscure results to a large extent, only sometimes altering statistical significance but rarely changing the direction of the response or general conclusions about bacterial disturbance dynamics. Although there may be instances where exDNA removal is essential for accurate representation of microbial communities, our study suggests these scenarios will be difficult to predict a priori. Overall, we found no evidence that certain time points across the distrubance were more affected by exDNA inclusion, nor did the size or composition of exDNA pools accurately predict when exDNA would alter significance levels. However, exDNA dynamics did vary strongly across the two soil types tested.

microbiology↗

bioRxiv2019

Stimulus-specific information flow across the canonical cortical microcircuit

The vast majority of mammalian neocortex consists of a stereotypical microcircuit, the canonical cortical microcircuit (CCM), consisting of a granular input layer, positioned between superficial and deep layers. Due to this uniform layout, neuronal activation tends to follow a similar laminar sequence, with unique information extracted at each step. For example, the primate primary visual cortex (V1) combines the two eyes signals, extracts stimulus orientation and modulates its activity depending on stimulus history. Several theories have been proposed on when and where these processes happen within the CCMs laminar activation sequence, but it has been methodologically challenging to test these hypotheses. Here, we use time-resolved multivariate pattern analysis (MVPA) to decode information regarding the eye-of-origin, stimulus orientation and stimulus repetition from simultaneously measured spiking responses across V1s laminar microcircuit. We find that eye-of-origin information was decodable for the entire duration of stimulus presentation, but diminished in the deepest layers of V1, consistent with the notion that two eyes signals are combined within the upper layers. Conversely, orientation information was transient and equally pronounced across the microcircuit, in line with the idea that this information is relayed to other areas for further processing. Moreover, when stimuli were repeated, information regarding orientation was enhanced at the expense of eye-of origin information, suggesting that V1 modulates information flow to optimize specific stimulus dimensions. Taken together, these findings provide empirical evidence that adjudicates between long-standing hypotheses and reveals how information transfer within the CCM supports unique cortical functions.\n\nSignificance StatementDespite the brains daunting complexity, there are common organizing principles across brain areas. For example, neocortical activation follows a stereotypical pattern that spreads from input layers towards layers above and below. While this activation pattern is well known, it has been challenging to ascertain how unique types of information are extracted within this common sequence in different brain areas. Here we use machine learning to track the flow of stimulus-specific information across the layers of visual cortex. We found that information regarding several separate stimulus dimensions was routed uniquely within the common activation sequence in a manner that confirmed prior model predictions. This finding demonstrates how differences in information flow within the stereotypical neocortical activation sequence shape area-specific functions.

neuroscience↗

bioRxiv2019

Experimental Evolution of the Megaplasmid pMPPla107 in Pseudomonas stutzeri Enables Identification of Genes Contributing to Sensitivity to an Inhibitory Agent

Horizontally transferred elements such as plasmids can, at times, burden host cells with various metabolic and fitness costs. Our previous work demonstrated that acquisition of the Pseudomonas syringae megaplasmid pMPPla107 causes sensitivity to a growth inhibiting substance that is produced in cultures during growth under standard laboratory conditions. After 500 generations of laboratory passage of P. stutzeri lines containing pMPPla107, two out of six independent lines displayed resistance to this inhibitory agent. We therefore sequenced the genomes of isolates from each independent evolutionary line to identify the genetic basis of this resistance phenotype through comparative genomics. Our analysis demonstrates that two different compensatory mutations on the megaplasmid ameliorate the sensitivity phenotype: 1) a large deletion of approximately 368kb in pMPPla107 and 2) a SNP in the gene we name skaA for Supernatant Killing Activity. These results provide further evidence that costs associated with horizontal gene transfer can be compensated through single mutational events and emphasize the power of experimental evolution and resequencing to better understand the genetic basis of evolved phenotypes.

microbiology↗

bioRxiv2018

Binocular modulation of monocular V1 neurons

In humans and other primates, sensory signals from each eye remain separated until they arrive in the primary visual cortex (V1), but their exact meeting point is unknown. In V1, some neurons are activated by stimulation of only one eye (monocular neurons) while most neurons are driven by stimulation of either eye (binocular neurons). Monocular neurons are most prevalent in the main input layers of V1 while binocular neurons dominate the layers above and below. This observation has given rise to the idea that the two eyes signals remain separate until they converge outside V1s input layers. Here, we show that despite responding to only one eye, monocular neurons in all layers, including the input layers, of V1 discriminate between stimulation of their driving eye alone and stimulation of both eyes. This finding suggests that binocular signals occur at an earlier processing stage than previously appreciated as even so-called monocular neurons across all V1 layers encode what is shown to both eyes.

neuroscience↗

bioRxiv2018

Adaptation of Intracortical Signaling Concurs with Enhanced Encoding Efficiency

Stimulus repetitions improve performance despite decreased brain responses, suggesting that the brain is more efficient when processing familiar stimuli. Previous work demonstrated that stimulus repetition enhances encoding efficiency in primary visual cortex (V1) by increasing synchrony and sharpening the orientation tuning of neurons. Here we show that these adaptive changes are supported by an altered flow of sensory activation across the V1 laminar microcircuit. Using a repeating stimulus sequence, we recorded laminar responses in V1 of two fixating monkeys. We found repetition-related response reductions that were most pronounced outside V1 layers that receive the main retinogeniculate input. This repetition-induced suppression was robust to alternating stimuli between the eyes, in line with the notion that repetition suppression is predominantly of cortical origin. Congruent with earlier reports, we found that V1 adaptation to repeating stimuli is accompanied by sharpened neural tuning as well as increased neural synchrony. Current source density (CSD) analysis, which provides an estimate of net synaptic activation, revealed that the responses to repeated stimuli were most profoundly affected within layers that harbor the bulk of cortico-cortical connections. Together, these results suggest that stimulus repetition induces an altered state of intracortical processing resulting in enhanced encoding efficiency of sensory stimuli.

neuroscience↗

bioRxiv2018

Binocular Integration Manifests as a Transient Spiking Increase Followed by Selective Suppression in Primary Visual Cortex

Research throughout the past decades revealed that neurons in primate primary visual cortex (V1) rapidly integrate the two eyes separate signals into a combined binocular response. The exact mechanisms giving underlying this binocular integration remain elusive. One open question is whether binocular integration occurs at a single stage of sensory processing or in a sequence of computational steps. To address this question, we examined the temporal dynamics of binocular integration across V1s laminar microcircuit of awake behaving monkeys. We find that V1 processes binocular stimuli in a dynamic sequence that comprises at least two distinct phases: A transient phase, lasting 50-150ms from stimulus onset, in which neuronal population responses are significantly enhanced for binocular stimulation compared to monocular stimulation, followed by a sustained phase characterized by widespread suppression in which feature-specific computations emerge. In the sustained phase, incongruent binocular stimulation resulted in response reduction relative to monocular stimulation across the V1 population. By contrast, sustained responses for binocular congruent stimulation were either reduced or enhanced relative to monocular responses depending on the neurons selectivity for one or both eyes (i.e., ocularity). These results suggest that binocular integration in V1 occurs in at least two sequential steps, with an initial additive combination of the two eyes signals followed by the establishment of interocular concordance and discordance.\n\nSignificance StatementOur two eyes provide two separate streams of visual information that are merged in the primary visual cortex (V1). Previous work showed that stimulating both eyes rather than one eye may either increase or decrease activity in V1, depending on the nature of the stimuli. Here we show that V1 binocular responses change over time, with an early phase of general excitation and followed by stimulus-dependent response suppression. These results provide important new insights into the neural machinery that supports the combination of the two eyes perspectives into a single coherent view.

neuroscience↗