Circuits for active vision : parallel tectothalamocortical visual pathways in the mouse.

Vision is a critical sensation for the interaction between humans and their surrounding environment. The eyes connect with the brain via retinal ganglion cell axons, which transmit visual sensory information from the periphery into the central nervous system for further processing, eventually leading to visual perception and the visual guidance of movement. Two main targets of retinal axons are the superior colliculus (SC) and the dorsal thalamus. From the SC, visual information is conveyed to the dorsal thalamus, and from the dorsal thalamus visual information is conveyed to the cortex, striatum and amygdala. This dissertation is focused on the functional properties of two parallel pathways from the SC to the dorsal thalamus: a pathway from the SC to the retinorecipient dorsolateral geniculate nucleus (dLGN) to the cortex, and a pathway from the SC to the pulvinar nucleus to the cortex. The experiments described in this dissertation used viral vector injections, tract tracing, in vitro whole cell patch clamp, optogenetics, electron and confocal microscopy, transgenic mouse lines and immunohistochemical staining techniques to elucidate the roles of the SC-dLGN-cortex pathway and SC-pulvinar-cortex pathway in visual coding. The first series of experiments revealed that SC and retinal inputs converge to innervate the proximal dendrites of cells in the dorsolateral shell of the dLGN that project to layer I of the striate cortex. The second series of experiments revealed the organization of subdivisions of the pulvinar nucleus in relation to inputs from the SC. The final series of experiments revealed the distribution and ultrastructure of pulvinocortical terminals, and identified the cell types activated by pulvinocortical synapses. Major targets of pulvinocortical terminals were identified as corticostriatal cells, suggesting that pulvinar acts as a hub connecting the SC, cortex and striatum

Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits.

BackgroundThere are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. This functional specificity is derived from distinct RGC morphologies and selective synapse formation with other retinal cell types; yet, how these properties are established during development remains unclear. Islet2 (Isl2) is a LIM-homeodomain transcription factor expressed in the developing retina, including approximately 40% of all RGCs, and has previously been implicated in the subtype specification of spinal motor neurons. Based on this, we hypothesized that Isl2+ RGCs represent a related subset that share a common function.ResultsWe morphologically and molecularly characterized Isl2+ RGCs using a transgenic mouse line that expresses GFP in the cell bodies, dendrites and axons of Isl2+ cells (Isl2-GFP). Isl2-GFP RGCs have distinct morphologies and dendritic stratification patterns within the inner plexiform layer and project to selective visual nuclei. Targeted filling of individual cells reveals that the majority of Isl2-GFP RGCs have dendrites that are monostratified in layer S3 of the IPL, suggesting they are not ON-OFF direction-selective ganglion cells. Molecular analysis shows that most alpha-RGCs, indicated by expression of SMI-32, are also Isl2-GFP RGCs. Isl2-GFP RGCs project to most retino-recipient nuclei during early development, but specifically innervate the dorsal lateral geniculate nucleus and superior colliculus (SC) at eye opening. Finally, we show that the segregation of Isl2+ and Isl2- RGC axons in the SC leads to the segregation of functional RGC types.ConclusionsTaken together, these data suggest that Isl2+ RGCs comprise a distinct class and support a role for Isl2 as an important component of a transcription factor code specifying functional visual circuits. Furthermore, this study describes a novel genetically-labeled mouse line that will be a valuable resource in future investigations of the molecular mechanisms of visual circuit formation

The representation of the visual field on the sub-cortical centers of the cat and rabbit

In the visual system the primary problem has been the identification of the visual pathway - the fiber systems along which the impulses arising in the eyes pass to the various subcortical levels and finally to the cortex - their precise localization, boundaries, and the extent of the terminal areas of the pathway. The second problem has been to determine whether, and to what extent, the original spatial and dimensional relationships present in visual space and in the retina are preserved in the pathways and centers, and if they are, how and where the various distinct areas of the retina, i.e. the fovea, the extra-foveal peripheral quadrants, the horizontal and vertical meridians, were represented in the various levels of the visual pathway

Signal processing in the tectothalamic pathway.

The pulvinar is the largest nucleus of the human dorsal thalamus and is affected in a variety of brain disorders, such as schizophrenia. The experiments described in this dissertation elucidate key features of tecto-pulvino-cortical pathways as a first step toward understanding their role in coding visual stimuli and coordinating appropriate responsive actions. The tree shrew is used as the animal model because the visual structures of the tree shrew brain display many of the features of the primate brain, and the tectopulvinar pathways are particularly enhanced in this species. The connections formed between the tectorecipient pulvinar nucleus and cortex were explored using tract tracing, immunohistochemistry, light, confocal, and electron microscopy. It was found that the pulvinar nucleus is reciprocally connected to two regions of the temporal cortex. Pulvinocortical terminals were found to contact dendritic spines of pyramidal cells, potentially influencing corticocortical projections to the striate cortex. Corticopulvinar synapses were found to be formed distal to tectopulvinar synapses on the dendrites of pulvinar neurons, suggesting that pulvinar neurons integrate inputs from the SC and temporal cortex. The membrane properties of neurons in the tectorecipient pulvinar were compared to those of neurons of the tree shrew dorsal lateral geniculate nucleus (dLGN), using whole cell recordings in slices maintained in vitro, western blotting, stereology, and neuron modeling techniques. These studies revealed that, compared to the dLGN, pulvinar neurons express a higher density of low threshold transient (T-type) calcium channels resulting in a greater propensity to fire with bursts of action potentials. These bursts may serve to increase the influence of pulvinocortical connections and/or synchronize the activity patterns of the multiple targets of the pulvinar nucleus. Finally, the properties of tectopulvinar synapses were explored using in vitro whole cell recordings in brain slices, immunohistochemistry and confocal microscopy. The results of these experiments suggest that the tectopulvinar terminals form convergent connections on pulvinar neurons and contain the vesicle-tethering proteins synapsin I and synapsin II. We suggest that these features allow pulvinar neurons to relay a dynamic range of visual signals from the SC in order to initiate and guide the appropriate responsive actions

SPATIAL CUES AFFECT NEURAL RESPONSES TO ODDBALL PARADIGM IN THE RAT’S AUDITORY MIDBRAIN

The ability to detect novel sounds in a natural environment has behavioral significance. For instance, novel sounds are important for predation, predator avoidance as well as inter- and intraspecific communications. One of the methods used to study novelty detection is to record neural responses to oddball paradigm. An oddball paradigm is a train of acoustic stimuli in which an oddball sound (Odd) is occasional and randomly interleaved in an otherwise repetitively presented qualitatively different standard sound (Std). Neurons sensitive to novel sounds exist in auditory structures including the auditory midbrain. This study investigated whether neurons in the auditory midbrain use directional cues in the detection of novel sounds. Two free-field speakers were used to present an oddball paradigm. Meanwhile, action potential discharges were recorded from single neurons in the rat’s auditory midbrain. In reference to the frontal midline of an animal, the two sounds were either co-localized in front of the ear contralateral to the recording site, or spatially separated such that one sound was presented at the contralateral ear while the other sound was presented at a different location in the frontal azimuth. It was found that many IC neurons generated stronger responses to Odd than Std. Neurons with transient firing patterns increased their responses to Odd presented at the contralateral ear when Std in the same sequence of an oddball paradigm was presented at a location that was ipsilateral to the side of recording. In contrast, neurons with sustained firing typically did not change their response to the Odd sound at the contralateral ear regardless of the position of Std in the frontal azimuth. These findings suggest that transient neurons use directional cues to detect novel sounds under natural hearing conditions. The results provide insights into neuronal mechanisms underlying both auditory novelty detection and spatial hearing

Towards building a more complex view of the lateral geniculate nucleus: Recent advances in understanding its role

The lateral geniculate nucleus (LGN) has often been treated in the past as a linear filter that adds little to retinal processing of visual inputs. Here we review anatomical, neurophysiological, brain imaging, and modeling studies that have in recent years built up a much more complex view of LGN . These include effects related to nonlinear dendritic processing, cortical feedback, synchrony and oscillations across LGN populations, as well as involvement of LGN in higher level cognitive processing. Although recent studies have provided valuable insights into early visual processing including the role of LGN, a unified model of LGN responses to real-world objects has not yet been developed. In the light of recent data, we suggest that the role of LGN deserves more careful consideration in developing models of high-level visual processing

Amino Acids and N-acetyl-aspartyl-glutamate as Neurotransmitter Candidates in the Monkey Retinogeniculate Pathways

The lateral geniculate nucleus (LGNd) receives chemically identified inputs from brain stem structures, the thalamus and visual cortex. The identity of the neurotransmitter(s) in the retinal input, however, is unknown. To investigate the possibility that some amino acids and certain dipeptides, such as N-acetyl-aspartyl-glutamate (NAAG), fulfill this function, changes in their concentration were measured in the optic tract, parvocellular and magno-cellular segments of the LGNd, superior colliculus and visual cortex of six monkeys (Macaca fascicularis), seven days after right optic tractotomy. The LGNd was studied also in two additional macaques, three months after occipital lobectomy. Tissue was frozen within five minutes of death, regions were dissected with the micropunch technique, and substances were analyzed by HPLC. Of the ten compounds measured in the normal side, glutamate, glutamine, glycine, and alanine had homogeneous distributions. GABA was highest in the superior colliculus, cystathionine and NAAG decreased in the rostrocaudal direction, and N-acetyl-aspartate showed an opposite gradient of concentration. The heterogeneity in taurine and aspartate was less systematic. Optic tract section induced significant, large reductions in NAAG, glutamate and aspartate in the optic tract distal to the lesion. Significant decreases in NAAG, and to a lesser extent in glutamate, were observed in the LGNd. Changes in the dipeptide were apparent in both the parvocellular and magnocellular segments. Reductions in glutamate reached significance in the parvocellular laminae, and those of aspartate approached significance in the magnocellular division. No significant differences were detected in the superior colliculus and striate cortex. Occipital lobectomy produced large declines in aspartate and glutamate in the LGNd, as well as moderate reductions in alanine and GABA, and minor changes in glutamine and glycine. The results of optic tractotomy support the role of NAAG as a neurotransmitter candidate in the monkey retinogeniculate pathways; its significant decrease in both geniculate segments suggests that X- and Y- retinal axons utilize this substance. Although at times the reductions in glutamate or aspartate failed to reach significance, their role cannot be excluded. The findings after occipital lobectomy strongly favor these latter substances as corticogeniculate transmitters