Temporal filtering of luminance and chromaticity in macaque visual cortex

The visibility of a periodic light modulation depends on its temporal frequency and spectral properties. Contrast sensitivity is highest at 8 to 10 Hz for modulations of luminance but is substantially lower for modulations between equiluminant lights. This difference between luminance and chromatic contrast sensitivity is rooted in retinal filtering, but additional filtering occurs in the cerebral cortex. To measure the cortical contributions to luminance and chromatic temporal contrast sensitivity, signals in the lateral geniculate nucleus (LGN) were compared to the behavioral contrast sensitivity of macaque monkeys. Long wavelength-sensitive (L) and medium wavelength-sensitive (M) cones were modulated in phase, to produce a luminance modulation (L+M), or in counterphase, to produce a chromatic modulation (L-M). The sensitivity of LGN neurons was well matched to behavioral sensitivity at low temporal frequencies but was approximately 7 times greater at high temporal frequencies. Similar results were obtained for L+M and L-M modulations. These results show that differences in the shapes of the luminance and chromatic temporal contrast sensitivity functions are due almost entirely to pre-cortical mechanisms. Simulations of cone photoreceptor currents show that temporal information loss in the retina and at the retinogeniculate synapse exceeds cortical information loss under most of the conditions tested.

Organization, Function, and Development of the Mouse Retinogeniculate Synapse

Visual information is encoded in distinct retinal ganglion cell (RGC) types in the eye tuned to specific features of the visual space. These streams of information project to the visual thalamus, the first station of the image-forming pathway. In the mouse, this connection between RGCs and thalamocortical neurons, the retinogeniculate synapse, has become a powerful experimental model for understanding how circuits in the thalamus are constructed to process these incoming lines of information. Using modern molecular and genetic tools, recent studies have suggested a more complex circuit organization than was previously understood. In this review, we summarize the current understanding of the structural and functional organization of the retinogeniculate synapse in the mouse. We discuss a framework by which a seemingly complex circuit can effectively integrate and parse information to downstream stations of the visual pathway. Finally, we review how activity and visual experience can sculpt this exquisite connectivity.

An evolving view of retinogeniculate transmission

The thalamocortical (TC) relay neuron of the dorsoLateral Geniculate Nucleus (dLGN) has borne its imprecise label for many decades in spite of strong evidence that its role in visual processing transcends the implied simplicity of the term “relay”. The retinogeniculate synapse is the site of communication between a retinal ganglion cell and a TC neuron of the dLGN. Activation of retinal fibers in the optic tract causes reliable, rapid, and robust postsynaptic potentials that drive postsynaptics spikes in a TC neuron. Cortical and subcortical modulatory systems have been known for decades to regulate retinogeniculate transmission. The dynamic properties that the retinogeniculate synapse itself exhibits during and after developmental refinement further enrich the role of the dLGN in the transmission of the retinal signal. Here we consider the structural and functional substrates for retinogeniculate synaptic transmission and plasticity, and reflect on how the complexity of the retinogeniculate synapse imparts a novel dynamic and influential capacity to subcortical processing of visual information.

Prolonged synaptic currents increase relay neuron firing at the developing retinogeniculate synapse

The retinogeniculate synapse, the connection between retinal ganglion cells (RGC) and thalamic relay neurons, undergoes robust changes in connectivity over development. This process of synapse elimination and strengthening of remaining inputs is thought to require synapse specificity. Here we show that glutamate spillover and asynchronous release are prominent features of retinogeniculate synaptic transmission during this period. The immature excitatory postsynaptic currents exhibit a slow decay time course that is sensitive to low-affinity glutamate receptor antagonists and extracellular calcium concentrations, consistent with glutamate spillover. Furthermore, we uncover and characterize a novel, purely spillover-mediated AMPA receptor current from immature relay neurons. The isolation of this current strongly supports the presence of spillover between boutons of different RGCs. In addition, fluorescence measurements of presynaptic calcium transients suggest that prolonged residual calcium contributes to both glutamate spillover and asynchronous release. These data indicate that, during development, far more RGCs contribute to relay neuron firing than would be expected based on predictions from anatomy alone.

Changes in input strength and number are driven by distinct mechanisms at the retinogeniculate synapse

Recent studies have demonstrated that vision influences the functional remodeling of the mouse retinogeniculate synapse, the connection between retinal ganglion cells and thalamic relay neurons in the dorsal lateral geniculate nucleus (LGN). Initially, each relay neuron receives a large number of weak retinal inputs. Over a 2- to 3-wk developmental window, the majority of these inputs are eliminated, and the remaining inputs are strengthened. This period of refinement is followed by a critical period when visual experience changes the strength and connectivity of the retinogeniculate synapse. Visual deprivation of mice by dark rearing from postnatal day (P)20 results in a dramatic weakening of synaptic strength and recruitment of additional inputs. In the present study we asked whether experience-dependent plasticity at the retinogeniculate synapse represents a homeostatic response to changing visual environment. We found that visual experience starting at P20 following visual deprivation from birth results in weakening of existing retinal inputs onto relay neurons without significant changes in input number, consistent with homeostatic synaptic scaling of retinal inputs. On the other hand, the recruitment of new inputs to the retinogeniculate synapse requires previous visual experience prior to the critical period. Taken together, these findings suggest that diverse forms of homeostatic plasticity drive experience-dependent remodeling at the retinogeniculate synapse.

Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse

Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (dl- threo-β-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.