Biology subjects

Moglie, M. J.

Publications and source records attributed to Moglie, M. J..

5 recordsLinked to original sources

bioRxiv2025

PhotoNeuro: A compact photodetector for synchronization of visual stimulus presentation during behavioral experiments in neuroscience.

Presenting visual stimuli in neuroscience experiments often requires the combination of analogue signals that carry information about the visual cue presented on the LCD display. Such signals are often sensed by photodetectors and recorded in analogue to digital converter (ADC) acquisition boards. The use of open-source visual programming languages such as Bonsai is becoming more and more popular. They are often used in combination with other open-source hardware such as Arduino development boards. These microcontroller-based boards can be used to automate behavioural experiments: e.g., actuate valves and motors and acquire analogue signals on their ADC channels. LCDs and other modern display allow fast presentation of arbitrary visual stimuli and are widely used for psychophysics and neuroscience experiments. However, most displays do not provide hardware timestamping options and are intrinsically nonlinear. Solving this limitation often requires a direct recording of the light emitted by the display with a photodiode. Such photodetectors are are often amplified at higher voltages and hard to integrate in most common recording systems that use microcontrollers. The other drawback commonly found by neuroscience researchers in commercial devices is the relatively big footprint that the sensor occupies on the screen which, ideally should be minimised so not to interfere with the stimuli presentation. In this paper we present a small footprint photodetector that can be easily replicated and operates at 5V making it suitable to use with common development boards and the visual programming language Bonsai that is commonly used for experiment creation and control. Additionally, we share a version that includes four photodiodes in small area (400 mm2). Specifications table O_TBL View this table: org.highwire.dtl.DTLVardef@7bafcforg.highwire.dtl.DTLVardef@5353ccorg.highwire.dtl.DTLVardef@a29f47org.highwire.dtl.DTLVardef@86f5d2org.highwire.dtl.DTLVardef@74da5f_HPS_FORMAT_FIGEXP M_TBL C_TBL

neuroscience↗

bioRxiv2025

Functional specialisation of multisensory temporal integration in the mouse superior colliculus

Our perception of the world depends on the brains ability to integrate information from multiple senses, with temporal disparities providing a critical cue for binding or segregating cross-modal signals1,2. The superior colliculus (SC) is a key site for integrating sensory modalities, but how cellular and network mechanisms in distinct anatomical regions within the SC contribute to multisensory integration remains poorly understood. Here, we recorded responses from over 5,000 neurons across the SCs anatomical axes of awake mice during presentations of spatially coincident audiovisual stimuli with varying temporal asynchronies. Our findings revealed that multisensory neurons reliably encoded audiovisual delays and exhibited nonlinear summation of auditory and visual inputs, with nonlinearities being more pronounced when visual stimuli preceded auditory stimuli, consistent with the natural statistics of light and sound propagation. Nonlinear summation was crucial for population-level decoding accuracy and precision of AV delay representation. Moreover, enhanced population decoding of audiovisual delays in the posterior-medial SC, facilitated temporal discriminability in the peripheral visual field. Cross-correlation analysis indicated higher connectivity in the medial SC and functional specific recurrent connectivity, with visual, auditory, and multisensory neurons preferentially connecting to other neurons of the same functional subclass, and multisensory neurons receiving approximately 50 percent of the total local input from other multisensory neurons. Our results highlight the interplay between single-neuron computations, network connectivity, and population coding in the SC, where nonlinear integration, distributed representations and regional functional specialisations enables robust sensory binding and supports the accurate encoding of temporal multisensory information. Our study provides new insights into how the brain leverages both single-neuron and network-level mechanisms to represent sensory features by adapting to the statistics of the natural world.

neuroscience↗

bioRxiv2020

Loss of choline agonism in the inner ear hair cell nicotinic acetylcholine receptor linked to the α10 subunit

The 910 nicotinic acetylcholine receptor (nAChR) plays a fundamental role in inner ear physiology. It mediates synaptic transmission between efferent olivocochlear fibers that descend from the brainstem and hair cells of the auditory sensory epithelium. The 9 and 10 subunits have undergone a distinct evolutionary history within the family of nAChRs. Predominantly in mammalian vertebrates, the 910 receptor has accumulated changes at the protein level that may ultimately relate to the evolutionary history of the mammalian hearing organ. In the present work we investigated the responses of 910 nAChRs to choline, the metabolite of acetylcholine degradation at the synaptic cleft. Whereas choline is a full agonist of chicken 910 receptors it is a partial agonist of the rat receptor. Making use of the expression of 910 heterologous receptors, encompassing wild-type, heteromeric, homomeric, mutant, chimeric and hybrid receptors, and in silico molecular docking, we establish that the mammalian (rat) 10 nAChR subunit underscores the reduced efficacy of choline. Moreover, we show that whereas the complementary face of the 10 subunit does not play an important role in the activation of the receptor by ACh, it is strictly required for choline responses. Thus, we propose that the evolutionary changes acquired in the mammalian 910 nAChR resulted in the loss of choline acting as a full agonist at the efferent synapse, without affecting the triggering of ACh responses. This may have accompanied the fine-tuning of hair cell post-synaptic responses to the high frequency activity of efferent medial olivocochlear fibers that modulate the cochlear amplifier. Contribution to the Field StatementIn the inner ear of mammals, several evolutionary changes have occurred resulting in an expansion of the hearing range to higher sound frequencies. Fine tuning of cochlear synapses is required for sound enconding. The synapse between efferent olivocochlear fibers, that descend from the hindbrain, and sensory hair cells modulates sound amplification at the periphery and it has been proposed as a major player in the expansion of the hearing range. The 910 nicotinic acetylcholine receptor, which mediates synaptic neurotransmission at the efferent fiber-hair cell synapses, has accumulated a high number of amino acid substitutions in the mammalian lineage. We now show that these evolutionary acquired changes have led to a mammalian receptor with a lower efficacy for choline, the metabolite produced at the synaptic cleft by acetylcholine degradation. Making use of molecular, electrophysiological and in silico simulations techniques we show that it is the 10 subunit the one responsible for the loss of full choline agonism on the efferent receptor in mammals. This functional change may prove fundamental to faithfully reproduce the high frequency activity of efferent medial olivocochlear fibers and the modulation of the cochlear amplifier.

neuroscience↗

bioRxiv2020

Synaptic contributions to cochlear outer hair cell Ca2+ homeostasis

For normal cochlear function, outer hair cells (OHCs) require a precise regulation of intracellular Ca2+ levels. Influx of Ca2+ occurs both at the stereocillia tips and through the basolateral membrane. In this latter compartment, two different origins for Ca2+ influx have been poorly explored: voltage-gated Ca2+ channels (VGCC) at synapses with type II afferent neurons, and 910 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in rodent OHCs, we report that these two Ca2+ entry sites are closely positioned, but present different regulation mechanisms. Ca2+ spread from MOC synapses is contained by cisternal Ca2+-ATPases. Considered a weak drive for transmitter release, we unexpectedly found that VGCC Ca2+ signals are comparable in size to those elicited by 910 and can be potentiated by ryanodine receptors. Finally, we showed that sorcin, a highly expressed gene product in OHCs with reported Ca2+ control function in cardiomy-ocytes, regulates basal Ca2+ levels and MOC synaptic activity in OHCs.

neuroscience↗

bioRxiv2019

Distinct evolutionary trajectories of neuronal and hair cell nicotinic acetylcholine receptors

The expansion and pruning of ion channel families has played a crucial role in the evolution of nervous systems. Remarkably, with a highly conserved vertebrate complement, nicotinic acetylcholine receptors (nAChRs) are unique among ligand-gated ion channels in that members of the family have distinct roles in synaptic transmission in non-overlapping domains, either in the nervous system, the inner ear hair cells or the neuromuscular junction. Here, we performed a comprehensive analysis of vertebrate nAChRs sequences, single cell expression patterns and comparative functional properties of receptors from three representative tetrapod species. We show that hair cell nAChRs underwent a distinct evolutionary trajectory to that of neuronal receptors. These were most likely shaped by different co-expression patterns and co-assembly rules of component subunits. Thus, neuronal nAChRs showed high degree of coding sequence conservation, coupled to greater co-expression variance and conservation of functional properties across tetrapod clades. In contrast, hair cell 910 nAChRs exhibited greater sequence divergence, narrow co-expression pattern and great variability of functional properties across species. These results point to differential substrates for random change within the family of gene paralogs that relate to the segregated roles of nAChRs in synaptic transmission.\n\nSignificance statementOur work exploits several peculiarities of the family of vertebrate nicotinic acetylcholine receptors (nAChRs) to explore the evolutionary trajectories of a ligand-gated ion channel family. By performing a comprehensive comparative analysis of nAChR subunits coding sequences, single cell expression patterns and functional properties we found a contrasting evolutionary history between nAChRs with widespread expression in the nervous system compared to those with isolated expression in the inner ear. Evolutionary changes were focused on differences in co-expression and co-assembly patterns for the former and coding sequences in the latter. This multidisciplinary approach provides further insight into the evolutionary processes that shaped the nervous and sensory systems of extant animals.

neuroscience↗