Biology subjects

Quinlan, M. A.

Publications and source records attributed to Quinlan, M. A..

3 recordsLinked to original sources

bioRxiv2026

A Caulobacter hub taxon in the soybean root endosphere has a distinctive biofilm and engages in riboflavin-mediated mutualism with Bradyrhizobium

While it is well established that communities of microbes colonize the surfaces of plants as epiphytes and the interior plant tissues as endophytes, their ecological roles and colonization mechanisms remain under characterized. Members of the genus Caulobacter have emerged as hub taxa in epiphytic and endophytic microbiomes of diverse plant hosts, but the factors that support their colonization and community interactions have not been defined. Here, we characterize Caulobacter sp. RL271, a non-canonical member of the genus recently identified as a hub taxon in the soybean root endosphere. We demonstrate that the surface attachment strategies and biofilm architecture of Caulobacter sp. RL271 are determined by a matrix of capsular polysaccharide and cellulose rather than a polar holdfast adhesin, a classical defining feature of the genus. Both polysaccharide components influence the kinetics of plant root colonization in the model plant Arabidopsis thaliana. We further demonstrate that the ecology of Caulobacter sp. RL271 is shaped by its nutritional dependence on exogenous riboflavin and by interactions with Bradyrhizobium diazoefficiens, the nitrogen-fixing symbiont of soybean roots. This work advances understanding of Caulobacter biology and establishes RL271 as a tractable model for dissecting the functional role of hub taxa in root endophyte communities.

microbiology↗

bioRxiv2026

Enhancer-based AAV approach for selective AADC delivery reduces motor symptoms and dyskinesia in Parkinson's mouse models

Degeneration of midbrain dopamine (DA) neurons and the resulting loss of striatal dopamine signaling are hallmarks of Parkinsons disease (PD). Although the dopamine precursor levodopa (L-DOPA) provides symptomatic relief, prolonged treatment often leads to abnormal involuntary movements (dyskinesia). Previous adeno-associated virus (AAV) approaches delivering aromatic L-amino acid decarboxylase (AADC) to the striatum under a ubiquitous promoter enhanced local dopamine synthesis and improved PD motor deficits, but this broad targeting strategy limited insight into the cellular populations underlying the behavioral improvements. Here, we engineered enhancer-driven AAVs to direct AADC expression to defined striatal and midbrain cell populations and paired these regulatory elements with a blood-brain barrier-penetrant capsid to enable both systemic and direct delivery. Targeted expression restored motor performance at reduced L-DOPA doses and decreased dyskinesia-like behaviors, producing improvements comparable to or greater than those achieved with ubiquitous expression. Distinct neuronal and non-neuronal populations each supported motor rescue but improved different behavioral domains to different extents, indicating complementary cell type-specific roles within PD-relevant circuits. Together, these findings establish enhancer-driven, cell type-specific AADC delivery as a better-tolerated strategy that enables rescue of motor deficits at lower L-DOPA doses in PD models.

neuroscience↗

bioRxiv2021

Intrinsic regulators of the action potential waveform control dopamine release to shape behavior

Despite the widely known role of dopamine in reinforcement learning, how the patterns of dopamine release that are critical to the acquisition, performance, and extinction of conditioned responses are generated is poorly resolved. Here, we demonstrate that the coordinated actions of two ion channels, Kv4.3 and BKCa1.1, control the pattern of dopamine neuron firing and dopamine release on different time scales to regulate separate phases of reinforced behavior in mice. Inactivation of Kv4.3 in VTA dopamine neurons increases ex vivo pacemaker activity and excitability that is associated with increased in vivo ramping dynamics prior to lever press in a learned instrumental response paradigm. Loss of Kv4.3 enhances performance of the learned response and facilitates extinction. In contrast, loss of BKCa1.1 increases burst firing and phasic dopamine release that enhances learning of an instrumental response. Inactivation of BKCa1.1 enhances extinction burst lever pressing in early extinction training that is associated with increased reward prediction error signals. These data demonstrate that temporally distinct patterns of dopamine release are governed by the intrinsic regulators of the cell to shape behavior. TeaserWe show that ion channels in midbrain dopamine neurons are critical for patterning action potential firing at the cell body and governing neurotransmitter release to regulate reinforcement learning.

neuroscience↗