Past events

The neural network of the retina processes the stream of visual signals falling onto the eye. When a visual image is presented to the retina, retinal ganglion cells, which form the output of this network, encode changes in local visual contrast inside their receptive fields. In natural vision, however, images do not arrive in isolation, but are structured in rapid sequences, separated by frequent saccades, which activate some types of ganglion cells and suppress others. Yet, little is known about how the rapid succession of images induced by saccades affects the encoding of spatial visual information. We found that a specific type of retinal ganglion cells, recorded in mouse retina, displays unexpected responses to saccade-like image transitions; the cells elicit a distinct spike burst when the same visual pattern reappears after the transition, providing a special code for such transitions or image parts that lead to a recurrence of stimulus patterns. This sensitivity to image recurrence is mediated by a circuit of serial inhibition, allowing a rapid reappearance of the image to suppress transition-induced inhibition of the ganglion cell. Our results show that saccade-like image transitions trigger interactions in the complex inhibitory network of the retina that lead to a dynamical gating of the information flow through the retina and provide a mode of operation that differs from the processing of simple, standard laboratory stimuli.

The analysis of spatial cells in the hippocampus and the medial entorhinal cortex has been a remarkable success story. Extracellular recordings have revealed astonishing functional abstractness in how single neurons encode concepts such as a place, direction, borders and grids. Though we know a great deal about these functional phenotypes of neuronal activation, information about their underlying microcircuits is sorely lacking. In this talk I will explore the structural underpinnings of this functional specificity in the superficial layers of the medial entorhinal cortex and what the components and architecture of the microcircuits involved in this reveal across evolution and development.

Abstract: The PNN is a specialized form of extracellular matrix, initially deposited around selected neurons during critical periods of development in specific parts of the brain, interrupted by holes where synapses occur. We postulate that the PNN comprises a longer-lived structural template and that new memories are created by cutting new holes in the PNN or by expanding existing holes to enable formation of new synapses or to strengthen existing ones. A basic premise of this hypothesis is that the PNN, should undergo very low metabolic renewal from the first age at which memories are retained until senescence, whereas the active constituents of synapses turn over much more frequently and would therefore be poorer substrates for permanent information storage, unless they are equipped with incredibly accurate copying mechanisms (R.Y.Tsien PNAS 2013). Experimental tests of the hypothesis: 1.PNN longevity; using 15N Spirulina diet for Stable Isotope Labeling in Mammals (SILAM) we compare the lifetimes of PNN proteins vs. synaptic components in Enriched Environment (EE) vs. Conventional Cages (CC), ending the pulse-chase by changing to 14N diet at P45. Analysis by Multidimensional Protein Identification Technology (MudPIT) of four different brain areas indicate: a. Low turnover rate for PNN proteins while synaptic proteins were at the noise level of 15N /14N ratio. b. Higher turnover of PNN proteins in EE vs. CC cages c.Variability in the retention of 15N in PNN proteins between brain areas. 2.Localization of the long-lasting proteins; Imaging of 15N /14N ratio using Nanoscale secondary ion mass spectrometry (nanoSIMS) localized and verified the MudPit finding that PNN turnover is very slow. 3. Spatial occupation of the PNN holes; 2 dimension electron microscopy (EM) and 3D volumes of Serial Block Face Scanning EM reveal that neurons engulfed in PNN have more than 95% of their plasma membrane surface occupied by PNN or synapses. 4. Inhibition of PNN holes modulation during strong memories acquisition; we examined the role and timing of matrix metalloproteinases (MMP) activity in memory consolidation using pharmacological inhibitors in a fear-conditioning paradigm. Our results demonstrate that MMP inhibition during fear induction: a. Does not affect acquisition b. Significantly impairs long-term memory (30 days) c. Is dose dependent d. That memory impairment increases with time. So far the hypothesis is supported by the results of the above tests.