Biology subjects

Ahmed, O. J.

Publications and source records attributed to Ahmed, O. J..

10 recordsLinked to original sources

bioRxiv2026

Rapid switching of in-phase and anti-phase interhemispheric rhythms within a single theta cycle: a mechanistic explanation

The granular retrosplenial cortex (RSG) supports memory consolidation and spatial navigation. In vivo recordings of local field potential (LFP) from RSG reveal coexisting gamma (30-80 Hz) and spline (100-160 Hz) oscillations, coupled to distinct phases of the background theta ([~]8 Hz) rhythm. Remarkably, bilateral recordings reveal that gamma and splines exhibit divergent interhemispheric phase relationships: gamma is in-phase across hemispheres, while splines are anti-phase. Here, using numerical bifurcation analysis of next-generation neural mass models, we show that RSG oscillations within a single hemisphere can be understood as alternation of PING (pyramidal-interneuron gamma) and ING (interneuron gamma) mechanisms in an excitatory-inhibitory network. Theta-frequency external drive to the inhibitory population switches the network between these two rhythms. Next, we build canonical interhemispheric circuits, composed of two such excitatory-inhibitory modules, delay-coupled across hemispheres. These circuits switch between in-phase gamma and anti-phase splines within a single theta cycle, reproducing the cross-spectral statistics of experimental RSG recordings. Finally, we present analytical results for threshold-linear neural mass models, showing cross-hemispheric phase patterning is governed by the ratio of cross-hemispheric delay to local inhibitory delay; we obtain explicit ranges of this ratio for which RSG-like patterning could be expected. Our work establishes that the unique oscillatory profile of RSG can be explained parsimoniously by minimal interhemispheric circuit configurations and provides a framework for experimental interrogation of interhemispheric rhythms.

neuroscience↗

bioRxiv2025

Neotenic expansion of adult-born dentate granule cells reconfigures GABAergic inhibition to enhance social memory consolidation

Adult-born dentate granule cells (abDGCs) contribute to hippocampal dentate gyrus (DG)-CA3/CA2 circuit functions in memory encoding, retrieval and consolidation. Heightened synaptic and structural plasticity of immature abDGCs is thought to govern their distinct contributions to circuit and network mechanisms of hippocampal-dependent memory operations. Protracted maturation or neoteny of abDGCs in higher mammals is hypothesized to offset decline in adult hippocampal neurogenesis by expanding the capacity for circuit and network plasticity underlying different memory operations. Here, we provide evidence for this hypothesis by genetically modelling the effective impact of neoteny of abDGCs on circuitry, network properties and social cognition in mice. We show that selective synchronous expansion of a single cohort of 4 weeks old immature, but not 8 weeks old mature abDGCs, increases functional recruitment of fast spiking parvalbumin expressing inhibitory interneurons (PV INs) in CA3/CA2, number of PV IN-CA3/CA2 synapses, and GABAergic inhibition of CA3/CA2. This transient increase in feed-forward inhibition in DG-CA2 decreased social memory interference and enhanced social memory consolidation. In vivo local field potential recordings revealed that the expansion of a single cohort of 4-week-old abDGCs increased baseline power, amplitude, and duration, as well as sensitivity to social investigation-dependent rate changes of sharp-wave ripples (SWRs) in CA1 and CA2, a neural substrate for memory consolidation. Inhibitory neuron-targeted chemogenetic manipulations implicate CA3/CA2 INs, including PV INs, as necessary and sufficient for social memory consolidation following neotenic expansion of the abDGC population and in wild-type mice, respectively. These studies suggest that neoteny of abDGCs may represent an evolutionary adaptation to support cognition by reconfiguring PV IN-CA3/CA2 circuitry and emergent network properties underlying memory consolidation.

neuroscience↗

bioRxiv2024

Psychedelic enhancement of flexible learning weeks after a single dose

Psychedelic drugs have shown therapeutic potential for the treatment of multiple neuropsychiatric disorders chiefly by promoting long-lasting plasticity in the prefrontal cortex (PFC). A critical function of the PFC is the ability to apply previously learned rules to novel scenarios, a skill known as cognitive flexibility. Here, we show that a single dose of 25CN-NBOH - a serotonin 2A receptor-preferring psychedelic - improves performance on a relatively complex flexible reversal learning task in mice, measured 2-3 weeks after the dose. This effect was seen in both male and female mice. This behavioral finding complements previous cellular results showing that a single psychedelic dose induces long-term structural changes in the PFC and uniquely demonstrates sustained improvements in cognitive flexibility in a novel behavioral paradigm weeks after the initial psychedelic dose in mice. This high throughput task also provides a rapid, automated way to assess other candidate psychedelics for their impact on cognitive flexibility in mice.

neuroscience↗

bioRxiv2024

Unique Transcriptomic Cell Types of the Granular Retrosplenial Cortex are Preserved Across Mice and Rats Despite Dramatic Changes in Key Marker Genes

The granular retrosplenial cortex (RSG) supports key functions ranging from memory consolidation to spatial navigation. The mouse RSG contains several cell types that are remarkably distinct from those found in other cortical regions. This includes the physiologically and transcriptomically unique low rheobase neuron that is the dominant cell-type in RSG layers 2/3 (L2/3 LR), as well as the similarly exclusive pyramidal cells that comprise much of RSG layer 5a (L5a RSG). While the functions of the RSG are extensively studied in both mice and rats, it remains unknown if the transcriptomically unique cell types of the mouse RSG are evolutionarily conserved in rats. Here, we show that mouse and rat RSG not only contain the same cell types, but key subtypes including the L2/3 LR and L5a RSG neurons are amplified in their representations in rats compared to mice. This preservation of cell types in male and female rats happens despite dramatic changes in key cell-type-specific marker genes, with the Scnn1a expression that selectively tags mouse L5a RSG neurons completely absent in rats. Important for Cre-driver line development, we identify alternative, cross-species genes that can be used to selectively target the cell types of the RSG in both mice and rats. Our results show that the unique cell types of the RSG are evolutionarily conserved across millions of years of evolution between mice and rats, but also emphasize stark species-specific differences in marker genes that need to be considered when making cell-type-specific transgenic lines of mice versus rats.

neuroscience↗

bioRxiv2024

Cell-type-specific cholinergic control of granular retrosplenial cortex with implications for angular velocity coding across brain states

Cholinergic receptor activation enables the persistent firing of cortical pyramidal neurons, providing a key cellular basis for theories of spatial navigation involving working memory, path integration, and head direction encoding. The granular retrosplenial cortex (RSG) is important for spatially-guided behaviors, but how acetylcholine impacts RSG neurons is unknown. Here, we show that a transcriptomically, morphologically, and biophysically distinct RSG cell-type - the low-rheobase (LR) neuron - has a very distinct expression profile of cholinergic muscarinic receptors compared to all other neighboring excitatory neuronal subtypes. LR neurons do not fire persistently in response to cholinergic agonists, in stark contrast to all other principal neuronal subtypes examined within the RSG and across midline cortex. This lack of persistence allows LR neuron models to rapidly compute angular head velocity (AHV), independent of cholinergic changes seen during navigation. Thus, LR neurons can consistently compute AHV across brain states, highlighting the specialized RSG neural codes supporting navigation.

neuroscience↗

bioRxiv2023

Cellular rules underlying psychedelic control of prefrontal pyramidal neurons

Classical psychedelic drugs are thought to increase excitability of pyramidal cells in prefrontal cortex via activation of serotonin 2A receptors (5-HT2ARs). Here, we instead find that multiple classes of psychedelics dose-dependently suppress intrinsic excitability of pyramidal neurons, and that extracellular delivery of psychedelics decreases excitability significantly more than intracellular delivery. A previously unknown mechanism underlies this psychedelic drug action: enhancement of ubiquitously expressed potassium "M-current" channels that is independent of 5-HT2R activation. Using machine-learning-based data assimilation models, we show that M-current activation interacts with previously described mechanisms to dramatically reduce intrinsic excitability and shorten working memory timespan. Thus, psychedelic drugs suppress intrinsic excitability by modulating ion channels that are expressed throughout the brain, potentially triggering homeostatic adjustments that can contribute to widespread therapeutic benefits.

neuroscience↗

bioRxiv2021

Sea of Electrodes Array (SEA): Extremely Dense and High-Count Silicon-Based Electrode Array Technology for High-Resolution High-Bandwidth Interfacing with 3D Neural Structures

In this work, we propose a new silicon-based micro-fabrication technology to fabricate 3D high-density high-electrode-count neural micro-probe arrays scalable to thousands and even millions of individual electrodes with user-defined length, width, shape, and tip profile. This unique technology utilizes DRIE of ultra-high aspect-ratio holes in silicon and refilling them with multiple films to form thousands of individual needles with metal tips making up the "sea-of-electrodes" array (SEA). World-record density of 400 electrodes/mm2 in a 5184-needle array is achieved. The needles are ~0.5-1.2mm long, <20m wide at the base, and <1m at the tip. The silicon-based structure of these 3D array probes with sharp tips, makes them stiff enough and easily implantable in the brain to reach a targeted region without failing. Moreover, the high aspect ratio of these extremely fine needles reduces the tissue damage and improves the chronic stability. Functionality of the electrodes is investigated using acute in vivo recording in a rat barrel field cortex under isoflurane anesthesia.

neuroscience↗

bioRxiv2020

Thalamus and claustrum control parallel layer 1 circuits in retrosplenial cortex

The granular retrosplenial cortex (RSG) is critical for both spatial and non-spatial behaviors, but the underlying neural codes remain poorly understood. Here, we use optogenetic circuit mapping in mice to reveal a double dissociation that allows parallel circuits in superficial RSG to process disparate inputs. The anterior thalamus and dorsal subiculum, sources of spatial information, strongly and selectively recruit small low-rheobase (LR) pyramidal cells in RSG. In contrast, neighboring regular-spiking (RS) cells are preferentially controlled by claustral and anterior cingulate inputs, sources of mostly non-spatial information. Precise sublaminar axonal and dendritic arborization within RSG layer 1, in particular, permits this parallel processing. Observed thalamocortical synaptic dynamics enable computational models of LR neurons to compute the speed of head rotation, despite receiving head direction inputs that do not explicitly encode speed. Thus, parallel input streams identify a distinct principal neuronal subtype ideally positioned to support spatial orientation computations in the RSG.

neuroscience↗

bioRxiv2020

Instantaneous amplitude and shape of postrhinal theta oscillations differentially encode running speed

Hippocampal theta oscillations have a temporally asymmetric waveform shape, but it is not known if this theta asymmetry extends to all other cortical regions involved in spatial navigation and memory. Here, using both established and improved cycle-by-cycle analysis methods, we show that theta waveforms in the postrhinal cortex are also temporally asymmetric. On average, the falling phase of postrhinal theta cycles lasts longer than the subsequent rising phase. There are, however, rapid changes in both the instantaneous amplitude and instantaneous temporal asymmetry of postrhinal theta cycles. These rapid changes in amplitude and asymmetry are very poorly correlated, indicative of a mechanistic disconnect between these theta cycle features. We show that the instantaneous amplitude and asymmetry of postrhinal theta cycles differentially encode running speed. Although theta amplitude continues to increase at the fastest running speeds, temporal asymmetry of the theta waveform shape plateaus after medium speeds. Our results suggest that the amplitude and waveform shape of individual postrhinal theta cycles may be governed by partially independent mechanisms and emphasize the importance of employing a single cycle approach to understanding the genesis and behavioral correlates of cortical theta rhythms.

neuroscience↗

bioRxiv2019

Uniquely excitable neurons enable precise and persistent information transmission through the retrosplenial cortex

The retrosplenial cortex (RSC) is essential for both memory and navigation, but the neural codes underlying these functions remain largely unknown. Here, we show that the most prominent cell type in layers 2/3 (L2/3) of the granular RSC is a uniquely excitable, small pyramidal cell. These cells have a low rheobase (LR), high input resistance, lack of spike-frequency adaptation, and spike widths intermediate to those of neighboring fast-spiking (FS) inhibitory neurons and regular-spiking (RS) excitatory neurons. LR cells are excitatory but rarely synapse onto neighboring neurons. Instead, L2/3 of RSC is an inhibition-dominated network with dense connectivity between FS cells and from FS to LR neurons. Biophysical models of LR but not RS cells precisely and continuously encode sustained input from afferent postsubicular head-direction cells. Thus, the unique intrinsic properties of LR neurons can support both the precision and persistence necessary to encode information over multiple timescales in the RSC.

neuroscience↗