Padala, A. | Search bioRxiv

bioRxiv2026

Insulin Growth Factor 1 affects glutamate receptor activity differently in primary cultures of neocortical versus hippocampal neurons

Insulin-like growth factor-1 (IGF-1) plays a critical role in neuronal signaling. Disrupted insulin/IGF-1 signaling is implicated in Alzheimers disease, among other conditions, yet its specific influence on glutamate receptor-mediated calcium responses remains unclear. We examined the impacts of IGF-1 on glutamate receptor function in primary rat neurons monitored for intraneuronal calcium following stimulation with glutamate, AMPA, or NMDA/glycine. Pharmacological blockers (CNQX for AMPA receptors, APV for NMDA receptors, and nimodipine for L-type calcium channels) were applied to define receptor-specific contributions. In hippocampal neurons, IGF-1 and insulin altered responses to glutamate in different directions, with IGF-1 tending to evoke and enhanced response. In neocortical neurons, by contrast, IGF-1 consistently reduced glutamate- and AMPA-evoked calcium peaks, suggesting an inhibitory effect on AMPA receptors. To rule out effects on voltage-gated calcium channels downstream of AMPA receptors, we tested effects of IGF-1 on depolarization with potassium chloride; calcium elevation in this case was unaffected by IGF-1. Likewise, IGF-1 did not inhibit responses to NMDA/glycine; and IGF-1 did not affect glutamate responses in the presence of CNQX, a selective AMPA receptor blocker. These findings, combined with the observation that IGF-1 effects persisted in the presence of APV (an NMDA receptor antagonist), indicate that the inhibition of glutamate responses by IGF-1 is mediated by suppression of AMPA receptor activity. IGF-1 may thus contribute to normal neurophysiology, and given the role that glutamate receptors play in excitotoxicity, IGF-1 may confer neuroprotection in the neocortex. Disruption of IGF-1 signaling, as seen in states resembling insulin resistance, may therefore worsen glutamate-driven excitotoxicity and contribute to adverse outcomes.

neuroscience↗

bioRxiv2025

Critical spatial separation at the scale of V1 receptive fields determines motion segmentation

Integrating elements that belong to a single object while segregating overlapping objects is a fundamental challenge for the visual system, exemplified by the phenomenon of motion transparency. While the middle temporal (MT) cortex is central to motion processing, the role of V1 in motion transparency remains controversial. It is still unclear at what spatial scale segmentation for motion transparency occurs. To address these questions, we conducted human psychophysics experiments using locally paired-dot stimuli moving in two directions separated by 90{degrees}. Subjects performed a 3AFC task to report whether the visual stimulus had no motion, a single direction, or two distinct directions. We systematically manipulated the path length of the dots, and therefore, the spatial separation between the paired dots, and the retinal eccentricity of the visual stimulus. We found that as the spatial separation between the paired dots increased, subjects perception shifted from a single direction to two distinct directions. Critically, we found that the spatial separation required for this perceptual transition increased with the eccentricity and closely matched the known receptive field sizes of V1 neurons at those eccentricities. Direction segmentation occurred only when the spatial separation between motion components exceeded the V1 receptive field size. Conversely, direction integration occurred when the spatial separation was smaller than the V1 receptive field size. Our results demonstrate that the receptive field size of V1 neurons sets the critical spatial scale for direction segmentation and suggest that V1 plays a key role in motion transparency and, more generally, in motion segmentation.

neuroscience↗