Biology subjects

Smirnakis, S. M.

Publications and source records attributed to Smirnakis, S. M..

5 recordsLinked to original sources

bioRxiv2018

Measuring single neuron visual receptive field sizes by fMRI

The non-invasive measurements of neuronal receptive field (RF) properties in-vivo allow a detailed understanding of brain organization as well as its plasticity by longitudinal following of potential changes. Visual RFs measured invasively by electrophysiology in animal models have traditionally provided a great extent of our current knowledge about the visual brain and its disorders. Voxel based estimates of population RF (pRF) by functional magnetic resonance imaging (fMRI) in humans revolutionized the field and have been used extensively in numerous studies. However, current methods cannot estimate single-neuron RF sizes as they reflect large populations of neurons with individual RF scatter. Here, we introduce a new approach to estimate RF size using spatial frequency selectivity to checkerboard patterns. This method allowed us to obtain non-invasive, single-unit, RF estimates in human V1 for the first time. These estimates were significantly smaller compared to prior pRF methods. Further, fMRI and electrophysiological experiments in non-human primates demonstrated an exceptional match validating the approach.

neuroscience↗

bioRxiv2018

Inhibitory Units: An Organizing Nidus for Feature-Selective Sub-Networks in Area V1.

Sensory stimuli are encoded by the joint firing of neuronal groups composed of pyramidal cells and interneurons, rather than single isolated neurons (Uhlhaas et al, 2009, Buzsaki, 2010). However, the principles by which these groups are organized to encode information remain poorly understood. A leading hypothesis is that similarly tuned pyramidal cells that preferentially connect to each other may form multi-cellular encoding units yoked to a similar purpose. The existence of such groups would be reflected on the profile of spontaneous events observed in neocortical networks. We used 2-photon calcium imaging to study spontaneous population-burst events in layer 2/3 of mouse area V1 during postnatal maturation (postnatal day 8-52). Throughout the period examined both size and duration of spontaneously occurring population-bursts formed scale-free distributions obeying a power law. The same was true for the degree of \"functional connectivity,\" a measure of pairwise synchrony across cells. These observations are consistent with a hierarchical small-world-net architecture, characterized by groups of cells with high local connectivity (\"small worlds\", cliques) connected to each other via a restricted number of \"hub\" cells\" (Bonifazi et al., 2009, Sporns, 2011, Luce & Perry, 1949). To identify candidate \"small world\" groups we searched for cells whose calcium events had a consistent temporal relationship to events recorded from local inhibitory interneurons. This was guided by the intuition that groups of neurons whose synchronous firing represents a \"temporally coherent computational unit\" (or feature) ought to be inhibited together. This strategy allowed us to identify clusters of pyramidal neurons whose firing is temporally \"linked\" to one or more local interneurons. These \"small-world\" clusters did not remain static, during postnatal development: both cluster size and overlap with other clusters decreased over time as pyramidal neurons became progressively more selective, \"linking\" to fewer neighboring interneurons. Notably, pyramidal neurons in a cluster show higher tuning function similarity than expected with each other and with their \"linked\" interneurons. Our findings suggest that spontaneous population events in the visual cortex are shaped by \"small-world\" networks of pyramidal neurons that share functional properties and work in concert with one or more local interneurons. We argue that such groups represent a fundamental neocortical unit of computation at the population level.

neuroscience↗

bioRxiv2018

Organization of Area hV5/MT+ in Subjects with Homonymous Visual Field Defects

Damage to the primary visual cortex (V1) leads to a visual field loss (scotoma) in the retinotopically corresponding part of the visual field. Nonetheless, a small amount of residual visual sensitivity persists within the blind field. This residual capacity has been linked to activity observed in the middle temporal area complex (V5/MT+). However, it remains unknown whether the organization of hV5/MT+ changes following V1 lesions. We studied the organization of area hV5/MT+ of five patients with dense homonymous defects in a quadrant of the visual field as a result of partial V1+ or optic radiation lesions. To do so, we developed a new method, which models the boundaries of population receptive fields directly from the BOLD signal of each voxel in the visual cortex. We found responses in hV5/MT+ arising inside the scotoma for all patients and identified two possible sources of activation: 1) responses might originate from partially lesioned parts of area V1 corresponding to the scotoma, and 2) responses can also originate independent of area V1 input suggesting the existence of functional V1-bypassing pathways. Apparently, visually driven activity observed in hV5/MT+ is not sufficient to mediate conscious vision. More surprisingly, visually driven activity in corresponding regions of V1 and early extrastriate areas including hV5/MT+ did not guarantee visual perception in the group of patients with post-geniculate lesions that we examined. This suggests that the fine coordination of visual activity patterns across visual areas may be an important determinant of whether visual perception persists following visual cortical lesions.

neuroscience↗

bioRxiv2017

Increased axonal bouton stability during learning in the mouse model of MECP2 duplication syndrome

MECP2-duplication syndrome is an X-linked form of syndromic autism caused by genomic duplication of the region encoding Methyl-CpG-binding protein 2. Mice overexpressing MECP2 demonstrate altered patterns of learning and memory, including enhanced motor learning. Previous work associated this enhanced motor learning to abnormally increased stability of dendritic spine clusters formed in the apical tuft of corticospinal, area M1, neurons during rotarod training. In the current study, we measure the structural plasticity of axonal boutons in Layer 5 (L5) pyramidal neuron projections to layer 1 of area M1 during motor learning. In wild-type mice we find that during rotarod training, bouton formation rate changes minimally, if at all, while bouton elimination rate doubles. Notably, the observed upregulation in bouton elimination with learning is absent in MECP2-duplication mice. This result provides further evidence of imbalance between structural stability and plasticity in this form of syndromic autism. Furthermore, the observation that axonal bouton elimination doubles with motor learning in wild-type animals contrasts with the increase of dendritic spine consolidation observed in corticospinal neurons at the same layer. This dissociation suggests that different area M1 microcircuits may manifest different patterns of structural synaptic plasticity during motor learning.\n\nSIGNIFICANCE STATEMENTAbnormal balance between synaptic stability and plasticity is a feature of several autism spectrum disorders, often corroborated by in vivo studies of dendritic spine turnover. Here we provide the first evidence that abnormally increased stability of axonal boutons, the presynaptic component of excitatory synapses, occurs during motor learning in the MECP2 duplication syndrome mouse model of autism. In contrast, in normal controls, axonal bouton elimination in L5 pyramidal neuron projections to layer 1 of area M1 doubles with motor learning. The fact that axonal projection boutons get eliminated, while corticospinal dendritic spines get consolidated with motor learning in layer 1 of area M1, suggests that structural plasticity manifestations differ across different M1 microcircuits.

neuroscience↗

bioRxiv2017

Excessive ERK-dependent synaptic clustering with enhanced motor learning in the MECP2 duplication syndrome mouse model of autism

Autism-associated genetic mutations may produce altered learning abilities by perturbing the balance between stability and plasticity of synaptic connections in the brain. Here we report an increase in the stabilization of dendritic spines formed during repetitive motor learning in the mouse model of MECP2-duplication syndrome, a high-penetrance form of syndromic autism. This increased stabilization is mediated entirely by spines that form cooperatively in clusters. The number of clusters formed and stabilized predicts the mutants enhanced motor learning and memory phenotype, reminiscent of savant-like behaviors occasionally associated with autism.\n\nThe ERK signaling pathway, which promotes cooperative plasticity between spines, was found to be hyperactive in MECP2-duplication motor cortex specifically after training. Inhibition of ERK signaling normalizes clustered spine stabilization and rescues motor learning behavior in mutants. We conclude that learning-associated dendritic spine clustering stabilized by hyperactive ERK signaling drives abnormal motor learning and memory consolidation in this model of syndromic autism.

neuroscience↗