Biology subjects

Alexandrou, G.

Publications and source records attributed to Alexandrou, G..

3 recordsLinked to original sources

bioRxiv2024

Layer Va neurons, as major presynaptic partners of corticospinal neurons, play critical roles in skilled movements

Corticospinal neurons (CSNs) are located in the cortex and projecting into the spinal cord. The activation of CSNs, which is associated with skilled motor behaviors, induces the activation of interneurons in the spinal cord. Eventually, motor neuron activation is induced by corticospinal circuits to coordinate muscle activation. Therefore, elucidating how the activation of CSNs in the brain is regulated is necessary for understanding the roles of CSNs in skilled motor behaviors. However, the presynaptic partners of CSNs in the brain remain to be identified. Here, we performed transsynaptic rabies virus-mediated brain-wide mapping to identify presynaptic partners of CSNs (pre-CSNs). We found that pre-CSNs are located in all cortical layers, but major pre-CSNs are located in layer Va. A small population of pre-CSNs are also located outside the cortex, such as in the thalamus. Inactivation of layer Va neurons in Tlx3-Cre mice results in deficits in skilled reaching and grasping behaviors, suggesting that, similar to CSNs, layer Va neurons are critical for skilled movements. Finally, we examined whether the connectivity of CSNs is altered after spinal cord injury (SCI). We found that unlike connections between CNSs and postsynaptic neurons, connections between pre-CSNs and CSNs do not change after SCI.

neuroscience↗

bioRxiv2022

A comparison between Mini-loop mediated isothermal amplification and polymerase spiral reaction for selective amplification of short template DNA

Isothermal amplification of circulating tumour-derived DNA (ctDNA) in the blood plasma could provide a rapid and cost effective alternative to PCR and NGS approaches for real-time cancer monitoring. Several variations of isothermal technologies exist, typically designed over unconstrained template length. Here, we compared the amplification efficiency of a compact loop mediated isothermal amplification reaction (termed AS-Mini-LAMP) with polymerase spiral reaction (PSR) suitable for analysis of ctDNA. Utilising 4-primers and targeting a 155 bp template encompassing the estrogen receptor (ESR1) c.1138G>C (p.E380Q) missense mutation. Using synthetic E380Q template DNA and Bst2.0 polymerase, results demonstrate that AS-Mini-LAMP was capable of selective mutant allele DNA amplification to a limit of 1,000 mutant copies, whereas no specific amplification was observed by PSR. The alternative use of Bst3.0 polymerase for either AS-Mini-LAMP or PSR revealed non-canonical events that underpin potentially misleading results when employing isothermal chemistries. In conclusion, AS-Mini-LAMP is more suited to mutation detection than PSR.

molecular biology↗

bioRxiv2020

Context-dependent odor learning requires the anterior olfactory nucleus

Learning to associate the context in which a stimulus occurs is an important aspect of animal learning. We propose that the association of an olfactory stimulus with its multisensory context is mediated by projections from ventral hippocampal networks (vHC) to the anterior olfactory nucleus (AON). Using a contextually-cued olfactory discrimination task, rats were trained to associate two olfactory stimuli with different responses depending on visuo-spatial context. Temporary lesions of the AON or vHC impaired performance on this task. In contrast, such lesions did not impair performance on a non-contextual olfactory discrimination task. Moreover, vHC lesions also impaired performance on an analogous contextually-cued texture discrimination task, whereas AON lesions affected only olfactory contextual associations. We describe a distinct role for the AON in olfactory processing, and conclude that early olfactory networks such as the olfactory bulb and AON function as multimodal integration networks rather than processing olfactory signals exclusively. Significance statementContextual information has long been known to play a key role in cognitive functions such as memory and decision making. We here show the contextual modulation of neural information in early primary sensory networks and its effects on contextually conditional learned behavior. We propose that projections from ventral hippocampus to anterior olfactory nucleus convey contextual information to the early olfactory system, modulating sensory representations and olfactory perception. Using behavioral pharmacology and computational modeling, we show how established network structures can mediate multimodal information and use context to make olfactory decisions.

neuroscience↗