Biology subjects

Kuruppath, P.

Publications and source records attributed to Kuruppath, P..

6 recordsLinked to original sources

bioRxiv2025

Connexin 36-mediated gap junctions contribute to fine odor discrimination and excitation of mitral cells in the mouse olfactory bulb

Key PointsO_LIThe output MCs of the olfactory bulb (OB) engage in strong electrical coupling via connexin 36 (Cx36)-mediated gap junctions. However, the behavioral and physiological relevance of these gap junctions is not well understood. C_LIO_LIIn studies conducted in Cx36 knock-out (KO) mice, we found that the mice displayed reduced fine odor discrimination capabilities versus wild-type mice in a go/no-go associative learning task. These results provide the first evidence to date of olfactory behavioral deficits in Cx36 KO mice. C_LIO_LIIn OB slices, Cx36 KO reduced excitatory responses in MCs to electrical stimulation of sensory afferents, especially during latter stages of the response. C_LIO_LIWe suggest that KO-induced impairments in fine odor discrimination are linked to reduced late MC excitation due to the longer time that mice require to make difficult odor discriminations. C_LI The output mitral cells (MCs) and tufted cells (TCs) of the mammalian olfactory bulb (OB) are coupled through both chemical mechanisms as well as gap junctions that are mediated by connexin 36 (Cx36). Here we tested both behavioral and physiological effects of eliminating gap junctions in knockout (KO) mice with homozygous deletions of Cx36. In a go/no-go associative learning task, Cx36 KO mice were found to display reduced discrimination capabilities when presented with pairs of stimuli that included a monomolecular odor and mixtures that had the same monomolecular odor and a small amount of a structurally similar odor. The impairments did not occur for less similar odor pairs, suggesting that Cx36 KO mice have olfactory processing deficits that are specific to fine odor discrimination. In physiological recordings in OB slices from Cx36 KO mice, MCs displayed reduced excitation in response to electrical stimulation of sensory afferents, both single stimulus pulses as well as a theta burst pattern designed to mimic sniffing. The reduction in MC excitatory current was most prominent for late portions of their response, 300 ms after single stimulus pulses or following all theta bursts that came after the first. More global local field potentials recorded in OB glomeruli were largely unaffected by Cx36 KO. We suggest that the KO-induced impairments in fine odor discrimination are linked to reduced late MC excitation due to the longer time that mice require to make difficult odor discriminations.

neuroscience↗

bioRxiv2025

In-vivo optogenetic manipulation approach for gerbil medial nucleus of trapezoid body

PurposeThis study introduces an in-vivo optogenetic manipulation approach for the medial nucleus of the trapezoid body (MNTB) in Mongolian gerbils, a species with a hearing range similar to humans. The MNTB is crucial for sound localization, but traditional methods lack temporal precision and reversibility. The aim of this study is to develop a specific, reversible method for controlling MNTB activity with fast and precise temporal control, an approach vital for studying sound localization. MethodsWe stereotactically injected adeno-associated viral vectors encoding opsins into the gerbil MNTB. Precise targeting was achieved despite the MNTBs location in a deep, heavily myelinated area of the brainstem. Opsin expression was confirmed via confocal microscopy. In-vivo electrophysiology combined with optical stimulation was used to test optical activation and suppression of MNTB activity during sound stimuli. ResultsOpsin expression was strong and stable in MNTB neurons over weeks and months. Laser stimulation during in-vivo recordings successfully induced both activation and suppression of MNTB neurons, demonstrating fast and precise control over neural activity. ConclusionThis in-vivo optogenetic method provides specific, reversible control of MNTB activity in gerbils with rapid, real-time modulation. It offers a powerful tool for investigating sound localization and auditory processing with high temporal precision.

neuroscience↗

bioRxiv2024

Integrating Optogenetic Stimulation of Olfactory Bulb Glomeruli with Foot Shock Fear Conditioning: A Robust Method for Investigating Olfactory-based Fear Conditioning

The integration of optogenetic techniques with traditional behavioral paradigms has provided novel insights into the neural mechanisms underlying olfactory-based fear conditioning. Olfactory cues are potent triggers for fear responses, and understanding the intricate neural dynamics involved in olfactory fear learning is crucial for unraveling the complexities of aversive memory formation. In this study, a robust method is presented that combines optogenetic stimulation of olfactory bulb glomeruli with foot shock fear conditioning to investigate olfactory-based fear learning in mice. By merging optogenetic manipulation with behavioral assays, a comprehensive framework for studying the mechanisms of olfactory fear conditioning is provided. This method offers new avenues for exploring the neural dynamics of adaptive responses to olfactory threats and may have implications for understanding fear-related disorders.

neuroscience↗

bioRxiv2023

Hyperexcitability in the olfactory bulb and impaired fine odor discrimination in the Fmr1 KO mouse model of fragile X syndrome

Fragile X syndrome (FXS) is the single most common monogenetic cause of autism spectrum disorders in humans. FXS is caused by loss of expression of the Fragile X mental retardation protein (FMRP), an mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation. Sensory processing deficits have been a major focus of studies of FXS in both humans and rodent models of FXS, but olfactory deficits remain poorly understood. Here we conducted experiments in wild-type and Fmr1 KO (Fmr1-/y) mice (males) that lack expression of the gene encoding FMRP to assess olfactory circuit and behavioral abnormalities. In patch-clamp recordings conducted in slices of the olfactory bulb, output mitral cells (MCs) in Fmr1 KO mice displayed greatly enhanced excitation, as evidenced by a much higher rate of occurrence of spontaneous network-level events known as long-lasting depolarizations (LLDs). The higher probability of LLDs did not appear to reflect changes in inhibitory connections onto MCs but rather enhanced spontaneous excitation of external tufted cells (eTCs) that provide feedforward excitation onto MCs within glomeruli. In addition, in a go/no-go operant discrimination paradigm, we found that Fmr1 KO mice displayed impaired discrimination of odors in difficult tasks that involved odor mixtures but not altered discrimination of monomolecular odors. We suggest that the higher excitability of MCs in Fmr1 KO mice may impair fine odor discrimination by broadening odor tuning curves of MCs and/or altering synchronized oscillations through changes in transient inhibition. Significance StatementFragile X syndrome (FXS) in humans is associated with a range of debilitating deficits including aberrant sensory processing. One sensory system that has received comparatively little attention in studies in animal models of FXS is olfaction. Here, we report the first comprehensive physiological analysis of circuit defects in the olfactory bulb in the commonly-used Fmr1 knockout (KO) mouse model of FXS. Our studies indicate that Fmr1 KO alters the local excitation/inhibition balance in the bulb - similar to what Fmr1 KO does in other brain circuits - but through a novel mechanism that involves enhanced feedforward excitatory drive. Furthermore, Fmr1 KO mice display behavioral impairments in fine odor discrimination, an effect that may be explained by enhanced neural excitability.

neuroscience↗

bioRxiv2020

The influence of stimulus duration on olfactory identity

Duration of a stimulus plays an important role in coding of sensory information. The role of stimulus duration is extensively studied in tactile, visual and auditory system. In the olfactory system, how the stimulus duration influences the identity of an olfactory information is not well understood. To test this, we activated the olfactory bulbs with blue light in mice expressing channelrhodopsin and behaviorally assessed the relevance of stimulus duration on olfactory identity. Our behavior data demonstrate that stimulus duration changes the olfactory information and the associated behavior.

neuroscience↗

bioRxiv2019

Functional relevance of dual olfactory bulb in olfactory coding

Bilateral convergence of external stimuli is a common feature of vertebrate sensory systems. This convergence of inputs from the bilateral receptive fields allows higher order sensory perception, such as depth perception in the vertebrate visual system and stimulus localization in the auditory system. The functional role of such bilateral convergence in the olfactory system is mostly unknown. To test whether each olfactory bulb contributes a separate piece of olfactory information, and whether information from the bilateral olfactory bulb is integrated, we synchronized the activation of olfactory bulbs with blue light in mice expressing channelrhodopsin in the olfactory sensory neurons and behaviorally assessed the relevance of dual olfactory bulb in olfactory perception. Our findings suggest that each olfactory bulb contributes separate components of olfactory information and mice integrate the olfactory information from each olfactory bulb to identify an olfactory stimulus. Significance statementIdentifying an odor is the first step in olfactory coding, as it is critical for the survival of most animals. Previous studies have shown that bilateral olfactory bulbs help rodents to localize the odor source and navigate accordingly. But It is still unclear whether the bilateral olfactory information plays any role in determining odor identity. Here for the first time, using optogenetics and behavioral experiments, we demonstrate that each olfactory bulb provides distinct olfactory information, and rodents integrate information from the two bulbs to identify an odor.

neuroscience↗