Biology subjects

Reynolds, J. N.

Publications and source records attributed to Reynolds, J. N..

3 recordsLinked to original sources

bioRxiv2026

Chronic subthreshold intermittent theta burst stimulation promotes structural axon initial segment plasticity in cortical neurons

Repetitive transcranial magnetic stimulation (rTMS) is used widely in neuroscience to study and alter neural plasticity. The cellular mechanisms underlying the effect of rTMS on the brain remain unclear but is primarily thought to act via activity-dependent synaptic plasticity mechanisms. Here we investigated whether chronic repetitive magnetic stimulation in vitro and in vivo can induce another form of activity-dependent neural plasticity, axon initial segment (AIS) plasticity. Cortical neurons isolated from postnatal wild-type mice were stimulated with 6 hours of sham, repetitive magnetic stimulation in the form of intermittent theta-burst stimulation (iTBS), or 15 mM potassium chloride, with changes to AIS location and length measured +0 hours and +24 hours post-stimulation. In addition, adult transgenic mice expressing green fluorescent protein at the AIS received daily sham or iTBS over the primary motor cortices for 7 consecutive days and processed for microscopy 3 hours after the last stimulation. Analysis of neurons stimulated in vitro showed that chronic iTBS caused bidirectional and time-dependent shifts to the AIS position relative to the soma and a delayed shortening of the AIS length at +24 hours. In the adult mice, 7 consecutive days of daily iTBS decreased AIS lengths in layers 2/3 and 5 pyramidal neurons. Our findings provide in vitro and in vivo evidence that rTMS induces neuronal plasticity outside of the synapse, which may contribute to the long-lasting effect of rTMS on the brain with repeated stimulation protocols.

neuroscience↗

bioRxiv2025

Characterisation of the axon initial segment and intrinsic excitability in the sub-acute phase post-ischemic stroke

BackgroundStroke is a leading cause of disability and stroke-induced changes in cortical excitability are thought to impede functional recovery. Identifying cellular targets that contribute to maladaptive excitability holds great potential for the development of therapeutic interventions to improve stroke outcomes. One potential target is the axon initial segment (AIS), the specialised cellular domain where action potentials are initiated. In the acute phase post stroke, neurons in the peri-infarct zone display abnormal AIS structural properties which is assumed to contribute to altered neuronal excitability. However, whether this continues into the sub-acute phase post stroke, a period with heightened plasticity and when physical rehabilitation typically begins is unknown. MethodsWe induced a photothrombotic ischemic stroke to the right motor cortex of 13-week-old mice alongside adeno-associated virus labelling of layer 2/3 and layer 5 pyramidal neurons in the peri-infarct zone and contralesional motor cortex. Immunofluorescence staining for Ankyrin-G and whole-cell patch clamp electrophysiology measures were made at 28-days post stroke to assess changes in AIS structure and function. Additionally, we investigated potential hemispheric-, cortical layer-, and sex-dependent differences in AIS and intrinsic excitability properties. ResultsWe found that normal AIS structure and function are preserved in the sub-acute phase post ischemic stroke. However, we found evidence of reduced input resistance across both hemispheres and reduced evoked spike firing frequency in the peri-infarct zone in both sexes. In addition, we found stroke reduced the evoked spike firing frequencies in the contralesional hemisphere, but only in males. ConclusionDespite the preservation of normal AIS structure and function in the sub-acute phase post ischemic stroke, cortical pyramidal neuron excitability is reduced through other intrinsic membrane mechanisms. Additionally, we show that changes to neuronal excitability spread to the contralesional hemisphere in males. These findings provide novel insight into the maladaptive changes to neural excitability in the sub-acute phase of ischemic stroke and further highlight the need to develop sex-specific stroke treatments.

neuroscience↗

bioRxiv2025

The superior colliculus gates dopamine responses to conditioned stimuli in visual classical conditioning

In classical Pavlovian conditioning, it is well-established that midbrain dopamine neurons respond to conditioned stimuli (CS) that predict a reward. However, how the dopamine neurons associate a neutral CS to a reward remains unknown. Here, we show that the superior colliculus (SC) develops neuronal responses to a visual CS during conditioning, which in turn drive the responses of dopamine neurons. Visual responses in the SC were only potentiated when a behaviorally meaningful time interval separated the visual stimulus and reward. Potentiation also required the convergence of visual, dopamine and serotonin inputs to the SC. Importantly, blocking potentiation of the visual response was sufficient to suppress the dopamine responses following a CS. These results reveal a mechanism for how the brain forms associations between unconditioned stimuli and behaviorally meaningful visual information during classical conditioning.

neuroscience↗