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Pham, T.

Publications and source records attributed to Pham, T..

3 recordsLinked to original sources

Electrical synapses regulate both subthreshold and population activity of principal cells in response to transient inputs within canonical feedforward circuits

As information about the world traverses the brain, the signals exchanged between neurons are passed and modulated by synapses, or specialized contacts between neurons. While neurotransmitter-based synapses tend to be either relay excitatory or inhibitory pulses of influence on the postsynaptic neuron, electrical synapses, composed of plaques of gap junction channels, are always-on transmitters that can either excite or inhibit a coupled neighbor. A growing body of evidence indicates that electrical synapses, similar to their chemical counterparts, are modified in strength during physiological neuronal activity. The synchronizing role of electrical synapses in neuronal oscillations has been well established, but their impact on transient signal processing in the brain is much less understood. Here we constructed computational models based on the canonical feedforward neuronal circuit, and included electrical synapses between inhibitory interneurons. We provided discrete closely-timed inputs to the circuits, and characterize the influence of electrical synapses on both the subthreshold summation and spike trains in the output neuron. Our simulations highlight the diverse and powerful roles that electrical synapses play even in simple circuits. Because these canonical circuits are represented widely throughout the brain, we expect that these are general principles for the influence of electrical synapses on transient signal processing across the brain.\n\nAuthor SummaryThe role that electrical synapses play in neural oscillations, network synchronization and rhythmicity is well established, but their role neuronal processing of transient inputs is much less understood. Here we used computational models of canonical feedforward circuits and networks to investigate how the strength of electrical synapses regulates the flow of transient signals passing through those circuits. We show that because the influence of electrical synapses on coupled neighbors can be either inhibitory or excitatory, their role in network information processing is heterogeneous.. Because of the widespread existence of electrical synapses between interneurons as well as a growing body of evidence for their plasticity, we expect such effects play a significant role in how the brain processes transient inputs.

neuroscience

A centrosome asymmetry switch in fly neural stem cells

Centrosomes, the main microtubule organizing centers (MTOCs) of metazoan cells, contain an older mother and a younger daughter centriole. Stem cells either inherit the mother or daughter centriole-containing centrosome, providing a possible mechanism for biased delivery of cell fate determinants. However, the dynamics and mechanisms regulating centrosome asymmetry and biased centrosome segregation are unclear. Using 3D-Structured Illumination Microscopy (3D-SIM) and live cell imaging we show that in fly neural stem cells (neuroblasts) the mitotic kinase Polo and its centriolar protein substrate Centrobin (Cnb) dynamically relocalize from the mother to the daughter centriole during mitosis. This mechanism generates a centrosome, containing two molecularly distinct centrioles by telophase. Cnbs timely relocalization is regulated by Polo-mediated phosphorylation whereas Polos daughter centriole enrichment requires both Wdr62 and Cnb. Based on optogenetic protein mislocalization experiments we propose that the establishment of centriole asymmetry in mitosis primes biased interphase MTOC activity, necessary for correct spindle orientation.

cell biology

Electrical synapses between inhibitory neurons shape the responses of principal neurons to transient inputs in the thalamus

As multimodal sensory information proceeds to the cortex, it is intercepted and processed by the nuclei of the thalamus. The main source of inhibition within thalamus is the reticular nucleus (TRN), which collects signals both from thalamocortical relay neurons and from thalamocortical feedback. Within the reticular nucleus, neurons are densely interconnected by connexin36-based gap junctions, known as electrical synapses. Electrical synapses have been shown to coordinate neuronal rhythms, including thalamocortical spindle rhythms, but their role in shaping or modulating transient activity is less understood. We constructed a four-cell model of thalamic relay and TRN neurons, and used it to investigate the impact of electrical synapses on closely timed inputs delivered to thalamic relay cells. We show that the electrical synapses of the TRN assist cortical discrimination of these inputs through effects of truncation, delay or inhibition of thalamic spike trains. We expect that these are principles whereby electrical synapses play similar roles in processing of transient activity in excitatory neurons across the brain.

neuroscience