Biology subjects

Alexander, P. C.

Publications and source records attributed to Alexander, P. C..

3 recordsLinked to original sources

bioRxiv2025

Biophysical Basis of the in vivo ERG of the Mouse: Rod, RPE and Müller glial Cell Contributions To Dark and to Light-driven Changes in Sub-Retinal Space o

The subretinal space (SRS) is a contiguous extracellular volume bounded by the external limiting membrane (ELM) and the retinal pigment epithelium (RPE). Approximately 90% of mouse rod photoreceptor dark current circulates in the SRS, and rod photoresponses materially alter SRS concentrations of permeant ions, especially K+. Following intravitreal injection of drugs that block glutamatergic synapses, and drugs that inhibit Kir4.1 and Kir7.1 channels expressed in Muller and RPE cells respectively, we measured electroretinograms (ERGs) in response to light flashes that completely suppress rod dark current, and compared ERG c-waves with predictions of a biophysical model of extracellular current sources generated by rod, Muller and RPE cells. SRS K+ fluxes in the dark steady-state were dominated by rods - NKX (-6.6 mM s-1), Kv2.1 channels (+5.4 mM s-1), NCKX (0.3 mM s-1) and HCN1 channel fluxes (1.0 mM s-1) - with much smaller contributions from Kir4.1 and Kir7.1 channels and trans-ELM and trans-RPE fluxes combining to zero net flux at resting SRS Ko of 5 mM (re 3.5 mM [K+] in blood plasma). In response to rod-saturating stimulation, Ko was predicted to decline to [~]3.5 mM with a half-time of [~] 0.5 s, driven mainly by a hyperpolarization-dependent decline in Kv2.1 current. The kinetics and amplitude of the c-wave are explained by the decline in SRS Ko, which negatively shifts the Nernst potential of apical RPE Kir7.1 channels, increasing outward current that sinks through the paracellular resistance to basal Bestrophin and CFTR chloride channels causing a trans-epithelial potential of [~] 2 mV.

biophysics↗

bioRxiv2025

Dynamic Modulation of Beta-Band Oscillations in the LGN and Their Role in Visual Processing

Neuronal oscillations are a ubiquitous feature of thalamocortical networks and can be dynamically modulated across processing states, enabling thalamocortical communication to flexibly adapt to varying environmental and behavioral demands. The lateral geniculate nucleus (LGN), like all thalamic nuclei, engages in reciprocal synaptic interactions with the cortex, relaying retinal information to and receiving feedback input from primary visual cortex (V1). While retinal excitation is the primary driver of LGN activity, retinal synapses represent a minority of the total synaptic input onto LGN neurons, allowing for both retinogeniculate and geniculocortical signals to be influenced by nonretinal sources. To gain a holistic view of network processing in the geniculocortical pathway, we performed simultaneous extracellular recordings from the LGN and V1 of behaving macaque monkeys, measuring local field potentials (LFPs) and spiking activity. These recordings revealed prominent beta-band oscillations coherent between the LGN and V1 that influenced spike timing in the LGN and were statistically consistent with a feedforward process from the LGN to V1. These thalamocortical oscillations were suppressed by visual stimulation, spatial attention, and behavioral arousal, strongly suggesting that these oscillations are not a feature of active visual processing. Instead, they appear analogous to occipital lobe, alpha oscillations recorded in humans and may represent a signature of signal suppression that occurs during periods of low engagement or active distractor suppression. Significance StatementOscillations within thalamocortical networks in the awake state are generally believed to enhance communication between the thalamus and cortex, allowing circuits to flexibly respond to changes in sensory, behavioral, and cognitive demands. Here, we show that oscillations within and between the LGN and V1 are suppressed by increases in visual stimulation, increases in behavioral arousal, and shifts in covert spatial attention. We therefore conclude that these oscillations are not a mechanism to enhance the transmission of retinal information through the LGN to V1. Instead, we propose that they are a signature of signal suppression that occurs when network engagement is low or during active distractor suppression.

neuroscience↗

bioRxiv2018

The augmentation of retinogeniculate communication during thalamic burst mode

Retinal signals are transmitted to cortex via neurons in the lateral geniculate nucleus (LGN), where they are processed in burst or tonic response mode. Burst mode occurs when LGN neurons are sufficiently hyperpolarized for T-Type Ca2+ channels to de-inactivate, allowing them to open in response to a depolarization which can trigger a high-frequency sequence of Na+-based spikes (i.e. burst). In contrast, T-type channels are inactivated during tonic mode and do not contribute to spiking. Although burst mode is commonly associated with sleep and the disruption of retinogeniculate communication, bursts can also be triggered by visual stimulation, thereby transforming the retinal signals relayed to the cortex.\n\nTo determine how burst mode affects retinogeniculate communication, we made recordings from monosynaptically connected retinal ganglion cells and LGN neurons in the cat during visual stimulation. Our results reveal a robust augmentation of retinal signals within the LGN during burst mode. Specifically, retinal spikes were more effective and often triggered multiple LGN spikes during periods likely to have increased T-Type Ca2+ activity. Consistent with the biophysical properties of T-Type Ca2+ channels, analysis revealed that effect magnitude was correlated with the duration of the preceding thalamic interspike interval and occurred even in the absence of classically defined bursts. Importantly, the augmentation of geniculate responses to retinal input was not associated with a degradation of visual signals. Together, these results indicate a graded nature of response mode and suggest that, under certain conditions, bursts facilitate the transmission of visual information to the cortex by amplifying retinal signals.\n\nSignificanceThe thalamus is the gateway for retinal information traveling to the cortex. The lateral geniculate nucleus (LGN), like all thalamic nuclei, has two classically defined categories of spikes--tonic and burst--that differ in their underlying cellular mechanisms. Here we compare retinogeniculate communication during burst and tonic response modes. Our results show that retinogeniculate communication is enhanced during burst mode and visually evoked thalamic bursts, thereby augmenting retinal signals transmitted to cortex. Further, our results demonstrate that the influence of burst mode on retinogeniculate communication is graded and can be measured even in the absence of classically defined thalamic bursts.

neuroscience↗