Stimulus contrast modulates burst activity in the lateral geniculate nucleus.

Burst activity is a ubiquitous feature of thalamic neurons and is well documented for visual neurons in the lateral geniculate nucleus (LGN). Although bursts are often associated with states of drowsiness, they are also known to convey visual information to cortex and are particularly effective in evoking cortical responses. The occurrence of thalamic bursts depends on (1) the inactivation gate of T-type Ca2+ channels (T-channels), which become de-inactivated following periods of increased membrane hyperpolarization, and (2) the opening of the T-channel activation gate, which has voltage-threshold and rate-of-change (δv/δt) requirements. Given the time/voltage relationship for the generation of Ca2+ potentials that underlie burst events, it is reasonable to predict that geniculate bursts are influenced by the luminance contrast of drifting grating stimuli, with the null phase of higher contrast stimuli evoking greater hyperpolarization followed by a larger dv/dt than the null phase of lower contrast stimuli. To determine the relationship between stimulus contrast and burst activity, we recorded the spiking activity of cat LGN neurons while presenting drifting sine-wave gratings that varied in luminance contrast. Results show that burst rate, reliability, and timing precision are significantly greater with higher contrast stimuli compared with lower contrast stimuli. Additional analysis from simultaneous recordings of synaptically connected retinal ganglion cells and LGN neurons further reveals the time/voltage dynamics underlying burst activity. Together, these results support the hypothesis that stimulus contrast and the biophysical properties underlying the state of T-type Ca2+ channels interact to influence burst activity, presumably to facilitate thalamocortical communication and stimulus detection.

Dynamics of Temporal Integration in the Lateral Geniculate Nucleus.

Before visual information from the retina reaches primary visual cortex (V1), it is dynamically filtered by the lateral geniculate nucleus (LGN) of the thalamus, the first location within the visual hierarchy at which nonretinal structures can significantly influence visual processing. To explore the form and dynamics of geniculate filtering we used data from monosynpatically connected pairs of retinal ganglion cells (RGCs) and LGN relay cells in the cat that, under anesthetized conditions, were stimulated with binary white noise and/or drifting sine-wave gratings to train models of increasing complexity to predict which RGC spikes were relayed to cortex, what we call "relay status." In addition, we analyze and compare a smaller dataset recorded in the awake state to assess how anesthesia might influence our results. Consistent with previous work, we find that the preceding retinal interspike interval (ISI) is the primary determinate of relay status with only modest contributions from longer patterns of retinal spikes. Including the prior activity of the LGN cell further improved model predictions, primarily by indicating epochs of geniculate burst activity in recordings made under anesthesia, and by allowing the model to capture gain control-like behavior within the awake LGN. Using the same modeling framework, we further demonstrate that the form of geniculate filtering changes according to the level of activity within the early visual circuit under certain stimulus conditions. This finding suggests a candidate mechanism by which a stimulus specific form of gain control may operate within the LGN.

Discovering Precise Temporal Patterns in Large-Scale Neural Recordings through Robust and Interpretable Time Warping.

Though the temporal precision of neural computation has been studied intensively, a data-driven determination of this precision remains a fundamental challenge. Reproducible spike patterns may be obscured on single trials by uncontrolled temporal variability in behavior and cognition and may not be time locked to measurable signatures in behavior or local field potentials (LFP). To overcome these challenges, we describe a general-purpose time warping framework that reveals precise spike-time patterns in an unsupervised manner, even when these patterns are decoupled from behavior or are temporally stretched across single trials. We demonstrate this method across diverse systems: cued reaching in nonhuman primates, motor sequence production in rats, and olfaction in mice. This approach flexibly uncovers diverse dynamical firing patterns, including pulsatile responses to behavioral events, LFP-aligned oscillatory spiking, and even unanticipated patterns, such as 7 Hz oscillations in rat motor cortex that are not time locked to measured behaviors or LFP.

Contrast gain control and retinogeniculate communication.

Visual information processed in the retina is transmitted to primary visual cortex via relay cells in the lateral geniculate nucleus (LGN) of the dorsal thalamus. Although retinal ganglion cells are the primary source of driving input to LGN neurons, not all retinal spikes are transmitted to the cortex. Here, we investigate the relationship between stimulus contrast and retinogeniculate communication and test the hypothesis that both the time course and strength of retinogeniculate interactions are dynamic and dependent on stimulus contrast. By simultaneously recording the spiking activity of synaptically connected retinal ganglion cells and LGN neurons in the cat, we show that the temporal window for retinogeniculate integration and the effectiveness of individual retinal spikes are inversely proportional to stimulus contrast. This finding provides a mechanistic understanding for the phenomenon of augmented contrast gain control in the LGN-a nonlinear receptive field property of LGN neurons whereby response gain during low-contrast stimulation is enhanced relative to response gain during high-contrast stimulation. In addition, these results support the view that network interactions beyond the retina play an essential role in transforming visual signals en route from retina to cortex.

Retinal and Nonretinal Contributions to Extraclassical Surround Suppression in the Lateral Geniculate Nucleus.

Extraclassical surround suppression is a prominent receptive field property of neurons in the lateral geniculate nucleus (LGN) of the dorsal thalamus, influencing stimulus size tuning, response gain control, and temporal features of visual responses. Despite evidence for the involvement of both retinal and nonretinal circuits in the generation of extraclassical suppression, we lack an understanding of the relative roles played by these pathways and how they interact during visual stimulation. To determine the contribution of retinal and nonretinal mechanisms to extraclassical suppression in the feline, we made simultaneous single-unit recordings from synaptically connected retinal ganglion cells and LGN neurons and measured the influence of stimulus size on the spiking activity of presynaptic and postsynaptic neurons. Results show that extraclassical suppression is significantly stronger for LGN neurons than for their retinal inputs, indicating a role for extraretinal mechanisms. Further analysis revealed that the enhanced suppression can be accounted for by mechanisms that suppress the effectiveness of retinal inputs in evoking LGN spikes. Finally, an examination of the time course for the onset of extraclassical suppression in the LGN and the size-dependent modulation of retinal spike efficacy suggests the early phase of augmented suppression involves local thalamic circuits. Together, these results demonstrate that the LGN is much more than a simple relay for retinal signals to cortex; it also filters retinal spikes dynamically on the basis of stimulus statistics to adjust the gain of visual signals delivered to cortex. SIGNIFICANCE STATEMENT: The lateral geniculate nucleus (LGN) is the gateway through which retinal information reaches the cerebral cortex. Within the LGN, neuronal responses are often suppressed by stimuli that extend beyond the classical receptive field. This form of suppression, called extraclassical suppression, serves to adjust the size tuning, response gain, and temporal response properties of neurons. Given the important influence of extraclassical suppression on visual signals delivered to cortex, we performed experiments to determine the circuit mechanisms that contribute to extraclassical suppression in the LGN. Results show that suppression is augmented beyond that provided by direct retinal inputs and delayed, consistent with polysynaptic inhibition. Importantly, these mechanisms influence the effectiveness of incoming retinal signals, thereby filtering the signals ultimately conveyed to cortex.