- The immunohistochemical distribution of the GABAA receptor α1, α2, α3, β2/3 and γ2 subunits in the human thalamus. [Journal Article]
- JCJ Chem Neuroanat 2017 Apr 23
- The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To det...
The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To determine which GABAA receptor subunit proteins are found in the human thalamus we investigated the distribution of five major GABAA receptor subunits α1, α2, α3, β2,3 and γ2 using immunohistochemical techniques. The α1-, β2,3- and γ2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups. The next most intense staining was for the α3-subunit followed by the α2-subunit. The intralaminar nuclear group, the mediodorsal nucleus and the thalamic reticular nucleus contained α1-, β2,3- and γ2- subunits staining as well as the highest levels of the α2- and α3- subunits. The sensory dorsal lateral geniculate nucleus contained very high levels of α1- and β2,3- and γ2-subunits. The highest densities of GABAA receptors found throughout the thalamus which contained the subunits α1, β2,3, and γ2 included nuclei which are especially involved in the control or the modulation of the cortico-basal ganglia-thalamo-cortical motor circuits and are thus important in disorders such as Huntington's disease where the GABAergic projections of the basal ganglia are compromised. In addition the majority of receptors in the thalamic reticular nucleus contain α3 and γ2 subunits whilst the intralaminar nuclei contain high levels of α2 and α3 subunits.
- Intracellular, in vivo, dynamics of thalamocortical synapses in visual cortex. [Journal Article]
- JNJ Neurosci 2017 Apr 24
- Seminal studies of the thalamocortical (TC) circuit in the visual system of the cat have been central to our understanding of sensory encoding. However, TC synaptic properties remain poorly understoo...
Seminal studies of the thalamocortical (TC) circuit in the visual system of the cat have been central to our understanding of sensory encoding. However, TC synaptic properties remain poorly understood. We used paired recordings, in the lateral geniculate nucleus (LGN) and primary visual cortex (V1), to provide the first in vivo characterization of sensory-driven TC potentials in V1. The amplitudes of EPSPs we characterized were smaller than those previously reported in vitro. Consistent with prior findings, connected LGN-V1 pairs were only found when their receptive fields (RFs) overlapped, and the probability of connection increased steeply with degree of RF overlap and response similarity. However, surprisingly, we found no relationship between EPSP amplitudes and the similarity of RFs or responses, suggesting different connectivity models for intracortical and thalamocortical circuits. Putative excitatory regular-spiking (RS) and inhibitory fast-spiking (FS) V1 cells had similar EPSP characteristics, showing that in the visual system, feedforward excitation and inhibition are driven with equal strength by the thalamus. Similar to observations in the somatosensory cortex, FS V1 cells received less specific input from LGN. Finally, orientation tuning in V1 was not inherited from single pre-synaptic LGN cells, and must therefore emerge exclusively from the combined input of all pre-synaptic LGN cells. Our results help to decipher early visual encoding circuits and have immediate utility in providing physiological constraints to computational models of the visual system.Significance Statement:In order to understand how the brain encodes the visual environment, we must understand the transfer of visual signals between various regions of the brain. Therefor, understanding synaptic dynamics is critical to our understanding of sensory encoding. This study provides the first characterization of visually evoked synaptic potentials between the visual thalamus and visual cortex in an intact animal. To record these potentials, we simultaneously recorded the extracellular potential of pre-synaptic thalamic cells and the intracellular potential of post-synaptic cortical cells in input layers of primary visual cortex. Our characterization of synaptic potentials in vivo disagreed with prior findings in vitro. This study will increase our understanding of thalamocortical circuits and will improve computational models of visual encoding.
- Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance. [Journal Article]
- NDNeural Dev 2017 Apr 24; 12(1):6
- CONCLUSIONS: These findings implicate Semaphorin-6A - Plexin-A2/Plexin-A4 interactions in dLGN axon guidance and in the spatiotemporal organization of guidepost cell populations in the mammalian subpallium.
- Modulating Lateral Geniculate Nucleus Neuronal Firing for Visual Prostheses: A Kalman Filter-based Strategy. [Journal Article]
- ITIEEE Trans Neural Syst Rehabil Eng 2017 Apr 17
- Developing visual prostheses that target inner brain structures along the visual pathway represent a new hope for patients with completely damaged early visual pathway sites. One of the major challen...
Developing visual prostheses that target inner brain structures along the visual pathway represent a new hope for patients with completely damaged early visual pathway sites. One of the major challenges in the development of subcortical and cortical visual prostheses is tuning electrical stimulation that could optimally induce desired visual percepts. In this paper, we propose a Kalman filter-based strategy that could be used to identify electrical stimulation patterns that mimic a specific visual input for thalamic visual prostheses. We demonstrate the performance of the proposed strategy using a population of LGN neurons modeled using an adapted Generalized Non-linear Model (GNM). A mean correlation of 0.69 is obtained between visually-evoked and electrically-evoked responses - driven using the proposed strategy - for an optimal electrode-placement setup. In addition, we demonstrate the performance for a random electrode-placement setup in which a mean correlation of 0.26 is obtained. For this latter setup, our analysis reveals an inversely proportional relationship between the obtained correlation and the distance between each neuron and the nearest electrode. The proposed strategy could be thus utilized to tune and enhance the performance of thalamic visual prostheses as well as other prosthesis systems.
- Fast and Slow Inhibition in the Visual Thalamus Is Influenced by Allocating GABAA Receptors with Different γ Subunits. [Journal Article]
- FCFront Cell Neurosci 2017; 11:95
- Cell-type specific differences in the kinetics of inhibitory postsynaptic conductance changes (IPSCs) are believed to impact upon network dynamics throughout the brain. Much attention has focused on ...
Cell-type specific differences in the kinetics of inhibitory postsynaptic conductance changes (IPSCs) are believed to impact upon network dynamics throughout the brain. Much attention has focused on how GABAA receptor (GABAAR) α and β subunit diversity will influence IPSC kinetics, but less is known about the influence of the γ subunit. We have examined whether GABAAR γ subunit heterogeneity influences IPSC properties in the thalamus. The γ2 subunit gene was deleted from GABAARs selectively in the dorsal lateral geniculate nucleus (dLGN). The removal of the γ2 subunit from the dLGN reduced the overall spontaneous IPSC (sIPSC) frequency across all relay cells and produced an absence of IPSCs in a subset of relay neurons. The remaining slower IPSCs were both insensitive to diazepam and zinc indicating the absence of the γ2 subunit. Because these slower IPSCs were potentiated by methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), we propose these IPSCs involve γ1 subunit-containing GABAAR activation. Therefore, γ subunit heterogeneity appears to influence the kinetics of GABAAR-mediated synaptic transmission in the visual thalamus in a cell-selective manner. We suggest that activation of γ1 subunit-containing GABAARs give rise to slower IPSCs in general, while faster IPSCs tend to be mediated by γ2 subunit-containing GABAARs.
- Robust information propagation through noisy neural circuits. [Journal Article]
- PCPLoS Comput Biol 2017 Apr 18; 13(4):e1005497
- Sensory neurons give highly variable responses to stimulation, which can limit the amount of stimulus information available to downstream circuits. Much work has investigated the factors that affect ...
Sensory neurons give highly variable responses to stimulation, which can limit the amount of stimulus information available to downstream circuits. Much work has investigated the factors that affect the amount of information encoded in these population responses, leading to insights about the role of covariability among neurons, tuning curve shape, etc. However, the informativeness of neural responses is not the only relevant feature of population codes; of potentially equal importance is how robustly that information propagates to downstream structures. For instance, to quantify the retina's performance, one must consider not only the informativeness of the optic nerve responses, but also the amount of information that survives the spike-generating nonlinearity and noise corruption in the next stage of processing, the lateral geniculate nucleus. Our study identifies the set of covariance structures for the upstream cells that optimize the ability of information to propagate through noisy, nonlinear circuits. Within this optimal family are covariances with "differential correlations", which are known to reduce the information encoded in neural population activities. Thus, covariance structures that maximize information in neural population codes, and those that maximize the ability of this information to propagate, can be very different. Moreover, redundancy is neither necessary nor sufficient to make population codes robust against corruption by noise: redundant codes can be very fragile, and synergistic codes can-in some cases-optimize robustness against noise.
- BIG1 is required for the survival of deep layer neurons, neuronal polarity, and the formation of axonal tracts between the thalamus and neocortex in developing brain. [Journal Article]
- PlosPLoS One 2017; 12(4):e0175888
- BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopat...
BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice and found that BIG1 regulates neurite outgrowth and brain development in vitro and in vivo. The loss of BIG1 decreased the size of the neocortex and hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs) and the interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL) neurons showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed from the piriform cortex (PIR), peaked in the neocortex, and then progressed into the hippocampus from embryonic day 13.5 (E13.5) to E17.5. The upper layer (UL) and DL order in the neocortex was maintained in BIG1-deficient mice, but the excitatory neurons tended to accumulate before their destination layers. Further pulse-chase migration assay showed that the migration defect was non-cell autonomous and secondary to the progression of apoptosis into the BIG1-deficient neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection of corticothalamic axons from the primary somatosensory cortex (S1) into the dorsal lateral geniculate nucleus (dLGN). The thalamocortical axons were unable to cross the diencephalon-telencephalon boundary (DTB). In vitro, BIG1-deficient neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also hypersensitive to low dose glutamate (5 μM), and died via apoptosis. This study showed the role of BIG1 in the survival of DL neurons in developing embryonic brain and in the generation of neuronal polarity.
- Temporal properties of colour opponent receptive fields in the cat lateral geniculate nucleus. [Journal Article]
- EJEur J Neurosci 2017 Apr 09
- The primordial form of mammalian colour vision relies on opponent interactions between inputs from just two cone types, "blue" (S-) and "green" (ML-) cones. We recently described the spatial receptiv...
The primordial form of mammalian colour vision relies on opponent interactions between inputs from just two cone types, "blue" (S-) and "green" (ML-) cones. We recently described the spatial receptive field structure of colour opponent blue-ON cells from the lateral geniculate nucleus of cats. Functional inputs from the opponent cone types were spatially coextensive and equally weighted, supporting their high chromatic and low achromatic sensitivity. Here, we studied relative cone weights, temporal frequency tuning and visual latency of cat blue-ON cells and non-opponent achromatic cells to temporally modulated cone-isolating and achromatic stimuli. We confirmed that blue-ON cells receive equally weighted antagonistic inputs from S- and ML-cones whereas achromatic cells receive exclusive ML-cone input. The temporal frequency tuning curves of S- and ML-cone inputs to blue-ON cells were tightly correlated between 1 Hz and 48 Hz. Optimal temporal frequencies of blue-ON cells were around 3 Hz, whereas the frequency optimum of achromatic cells was close to 10 Hz. Most blue-ON cells showed negligible response to achromatic flicker across all frequencies tested. Latency to visual stimulation was significantly greater in blue-ON than in achromatic cells. The S- and ML-cone responses of blue-ON cells had on average, similar latencies to each other. Altogether, cat blue-ON cells showed remarkable balance of opponent cone inputs. Our results also confirm similarities to primate blue-ON cells suggesting that colour vision in mammals evolved on the basis of a sluggish pathway that is optimised for chromatic sensitivity at a wide range of spatial and temporal frequencies. This article is protected by copyright. All rights reserved.
- Characterizing the effects of feature salience and top-down attention in the early visual system. [Journal Article]
- JNJ Neurophysiol 2017 Apr 05; :jn.00924.2016
- The visual system employs a sophisticated balance of attentional mechanisms: salient stimuli are prioritized for visual processing, yet observers can also ignore such stimuli when their goals require...
The visual system employs a sophisticated balance of attentional mechanisms: salient stimuli are prioritized for visual processing, yet observers can also ignore such stimuli when their goals require directing attention elsewhere. A powerful determinant of visual salience is local feature contrast: if a local region differs from its immediate surround along one or more feature dimensions, it will appear more salient. Here, we used high-resolution fMRI at 7T to characterize the modulatory effects of bottom-up salience and top-down voluntary attention within multiple sites along the early visual pathway, including visual areas V1-V4 and the lateral geniculate nucleus (LGN). Observers viewed arrays of spatially distributed gratings, where one of the gratings immediately to the left or right of fixation differed from all other items in orientation or motion direction, making it salient. To investigate the effects of directed attention, observers were cued to attend to the grating to the left or right of fixation, which was either salient or non-salient. Results revealed reliable additive effects of top-down attention and stimulus-driven salience throughout visual areas V1-hV4. In comparison, the LGN exhibited significant attentional enhancement but was not reliably modulated by orientation- or motion-defined salience. Our findings indicate that top-down effects of spatial attention can influence visual processing at the earliest possible site along the visual pathway, including the LGN, while the processing of orientation- and motion-driven salience primarily involves feature-selective interactions that take place in early cortical visual areas.
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- Visual perception skills: a comparison between patients with Noonan syndrome and 22q11.2 deletion syndrome. [Journal Article]
- GBGenes Brain Behav 2017 Apr 05
- Ventral and dorsal streams are visual pathways deputed to transmit information from the photoreceptors of the retina to the lateral geniculate nucleus and then to the primary visual cortex (V1). Seve...
Ventral and dorsal streams are visual pathways deputed to transmit information from the photoreceptors of the retina to the lateral geniculate nucleus and then to the primary visual cortex (V1). Several studies investigated whether one pathway is more vulnerable than the other during development, and whether these streams develop at different rates. The results are still discordant. The aim of the present study was to understand the functionality of the dorsal and the ventral streams in two populations affected by different genetic disorders, Noonan syndrome and 22q11.2 deletion syndrome, and explore possible genotype-phenotype relationships. "Form coherence" abilities for the ventral stream and "motion coherence" abilities for the dorsal stream were evaluated in 19 participants with Noonan syndrome, and 20 participants with 22q11.2 deletion syndrome. Collected data were compared to 55 age-matched controls. Participants with Noonan syndrome and 22q11.2 deletion syndrome did not differ in the Form Coherence task, and their performance was significantly lower than that of controls. However, in the Motion Coherence task, the group with Noonan syndrome and controls did not differ, and both obtained significantly higher scores than the group with 22q11.2 deletion syndrome. Our findings indicate that deficits in the dorsal stream are related to the specific genotype, and that in our syndromic groups the ventral stream is more vulnerable than the dorsal stream.