Biology subjects

Nolan, M. F.

Publications and source records attributed to Nolan, M. F..

8 recordsLinked to original sources

bioRxiv2025

Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes

Myelination facilitates the rapid conduction of action potentials along axons. In the central nervous system (CNS), myelinated axons vary over 100-fold in diameter, with conduction speed scaling linearly with increasing diameter. Axon diameter and myelination are closely interlinked, with axon diameter exerting a strong influence on myelination. Conversely, myelinating Schwann cells in the peripheral nervous system can both positively and negatively affect axon diameter. However, whether axon diameter is regulated by CNS oligodendrocytes is less clear. Here, we investigated CNS axon diameter growth in the absence of myelin using mouse (Mbpshi/shi and Myrf conditional knockout) and zebrafish (olig2 morpholino) models. We find that neither the ensheathment of axons, nor the formation of compact myelin are required for CNS axons to achieve appropriate and diverse diameters. This indicates that developmental CNS axon diameter growth is independent of myelination, and shows that myelinating cells of CNS and PNS differentially influence axonal morphology.

neuroscience↗

bioRxiv2023

Synaptic interactions between stellate cells and parvalbumin interneurons in layer 2 of the medial entorhinal cortex are organized at the scale of grid cell clusters

Interactions between excitatory and inhibitory neurons are critical to computations in cortical circuits but their organization is difficult to assess with standard electrophysiological approaches. Within the medial entorhinal cortex, representation of location by grid and other spatial cells involves circuits in layer 2 in which excitatory stellate cells interact with each other via inhibitory parvalbumin expressing interneurons. Whether this connectivity is structured to support local circuit computations is unclear. Here, we introduce strategies to address the functional organization of excitatory-inhibitory interactions using crossed Cre- and Flp-driver lines to direct targeted presynaptic optogenetic activation and postsynaptic cell identification. We then use simultaneous patch-clamp recordings from postsynaptic neurons to assess their shared input from optically activated presynaptic populations. We find that extensive axonal projections support spatially organized connectivity between stellate cells and parvalbumin interneurons, such that direct connections are often, but not always, shared by nearby neurons, whereas multisynaptic interactions coordinate inputs to neurons with greater spatial separation. We suggest that direct excitatory-inhibitory synaptic interactions may operate at the scale of grid cell clusters, with local modules defined by excitatory-inhibitory connectivity, while indirect interactions may coordinate activity at the scale of grid cell modules.

neuroscience↗

bioRxiv2023

Anchoring of grid fields selectively enhances localisation by path integration

Grid firing fields have been proposed as a neural substrate for spatial localisation in general or for path integration in particular. While there are theoretical arguments to support each possibility, it has been challenging to directly test whether and when grid cells contribute to behaviours. Here, we investigate firing of grid and non-grid cells in the medial entorhinal cortex during a location memory task. We find that grid firing can either be anchored to the task environment, or can encode distance travelled independently of the task reference frame. Anchoring varied between and within sessions, while spatial firing of non-grid cells was either coherent with the grid population, or was stably anchored to the task environment. We took advantage of the variability in task-anchoring to evaluate whether and when encoding of location by grid cells might contribute to behaviour. We find that when reward location is indicated by a visual cue performance is similar regardless of whether grid cells are task-anchored or not, arguing against a role for grid representations when location cues are available. By contrast, in the absence of the visual cue, performance was enhanced when grid cells were anchored to the task environment. Our results suggest that anchoring of grid cells to task reference frames selectively enhances performance when path integration is required.

neuroscience↗

bioRxiv2022

Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1

Standard models for spatial and episodic memory suggest that the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) send parallel independent inputs to the hippocampus, each carrying different types of information. Here, we evaluate the possibility that information is integrated between divisions of the entorhinal cortex prior to reaching the hippocampus. We demonstrate that fan cells in layer 2 (L2) of LEC that receive neocortical inputs, and that project to the hippocampal dentate gyrus, also send axon collaterals to layer 1 (L1) of the MEC. Activation of fan cell inputs evokes monosynaptic glutamatergic excitation of stellate and pyramidal cells in L2 of the MEC, typically followed by inhibition that contains fast and slow components mediated by GABAA and GABAB receptors, respectively. Fan cell inputs also directly activate interneurons in L1 and L2 of MEC, with synaptic connections from L1 interneurons accounting for slow feedforward inhibition of L2 principal cell populations. The relative strength of excitation and inhibition following fan cell activation differs substantially between neurons and is largely independent of anatomical location. Our results demonstrate that the LEC, in addition to directly influencing the hippocampus, can activate or inhibit major hippocampal inputs arising from the MEC. Thus, local circuits in the superficial MEC may combine spatial information with sensory and higher order signals from the LEC, providing a substrate for integration of what and where components of episodic memories.

neuroscience↗

bioRxiv2022

Single photon kilohertz frame rate imaging of neural activity

Establishing the biological basis of cognition and its disorders will require high precision spatiotemporal measurements of neural activity. Recently developed genetically encoded voltage indicators (GEVIs) report both spiking and subthreshold activity of identified neurons. However, maximally capitalising on the potential of GEVIs will require imaging at the millisecond time scales, which remains challenging with standard camera systems. Here we report application of single photon avalanche diode (SPAD) sensors to imaging neural activity at kilohertz frame rates. SPADs are electronic devices that when activated by a single photon cause an avalanche of electrons and a large electric current. We use an array of SPAD sensors to image individual neurons expressing genetically encoded voltage indicators. We show that subthreshold and spiking activity can be resolved with shot noise limited signals at frame rates of up to 10 kHz. SPAD imaging was able to reveal millisecond scale synchronisation of neural activity in an ex-vivo seizure model. SPAD sensors may have widespread applications for investigation of millisecond timescale neural dynamics. Table of contentsThe high temporal precision of single photon avalanche diodes (SPADs) is leveraged to record neural activity reported by genetically encoded voltage indicators. Sub-threshold and spiking activity of single neurons was resolved with shot noise limited signals at frame rates of up to 10 kHz. SPAD sensors may have widespread applications for neural imaging at high frame rates. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

neuroscience↗

bioRxiv2022

pyNeurode: a real-time neural signal processing framework

Accurate decoding of neural signals often requires assigning extracellular waveforms acquired on the same electrode to their originating neurons, a process known as spike sorting. While many offline sorters are available, accurate online sorting of spikes with many channels is still a challenging problem. Existing online sorters either use simple algorithms with low accuracy, can only process a handful of channels, or depend on a complex runtime environment that is difficult to set up. We have developed a state-of-the-art online spike sorting platform in Python that enables large-scale, fully automatic real-time spike sorting and decoding on hundreds of channels. Our system is cross-platform and works seamlessly with the Open Ephys suite of open-source hardware and software widely used in many neuroscience laboratories worldwide. It also comes with a user-friendly graphical user interface to monitor the cluster quality, spike waveforms and neuronal firing rate. Our platform has comparable accuracy to offline sorters and can achieve an end-to-end sorting latency of around 160 ms for 128-channel signals. It will be useful for research in fundamental neuroscience, closed-loop feedback neuromodulation and brain-computer interfaces.

neuroscience↗

bioRxiv2021

Analogue representation of a spatial memory by ramp-like neural activity in retrohippocampal cortex

Neurons in the retrohippocampal cortices play crucial roles in spatial memory. Many retrohippocampal neurons have firing fields that are selectively active at specific locations, with memory for rewarded locations associated with reorganisation of these firing fields. Whether this is the sole strategy for representing spatial memories is unclear. Here, we demonstrate that during a spatial memory task retrohippocampal neurons encode location through ramping activity that extends within segments of a linear track approaching and following a reward, with the rewarded location represented by offsets or switches in the slope of the ramping activity. These ramping representations could be maintained independently of trial outcome and cues that mark the reward location, indicating that they result from recall of the track structure. During recordings in an open arena, neurons that generated ramping activity during the spatial memory task were more numerous than grid or border cells, with a majority showing spatial firing that did not meet criteria for classification as grid or border representations. Encoding of rewarded locations through offsets and switches in the slope of ramping activity also emerged in recurrent neural networks trained to solve a similar location memory task. Impaired performance of these networks following disruption of outputs from ramping neurons is consistent with this coding strategy supporting navigation to recalled locations of behavioural significance. We hypothesise that retrohippocampal ramping activity mediates readout of learned models for goal-directed navigation.

neuroscience↗

bioRxiv2019

Fan cells in layer 2 of lateral entorhinal cortex are critical for episodic-like memory

The lateral entorhinal cortex (LEC) is a critical structure for episodic memory, but the roles of discrete neuronal populations within LEC are unclear. Here, we establish an approach for selectively targeting fan cells in layer 2 (L2) of LEC. Whereas complete lesions of the LEC were previously found to abolish associative recognition memory, we find that after selective suppression of synaptic output from fan cells mice still recognise novel object-context configurations, but are impaired in recognition of novel object-place-context associations. Our experiments suggest a segregation of memory functions within LEC networks and indicate that specific inactivation of fan cells leads to behavioural deficits reminiscent of early stages of Alzheimers disease.

neuroscience↗