Centre for Integrative Biology (CIBIO)
Neural stem cells and adult neurogenesis
From early neuronal polarity to establishment of neuronal connections in adult neurogenesis
The correct establishment of neuronal connections into neuronal circuitry is essential for the proper organization of the nervous systems. Such connections are generated through polarization of newly generated neurons beginning with the specification of a single axon among equally potential neurites.
Along this process, growth cones located at the leading edges of undifferentiated neurites detect and respond to environmental cues that guide one, and only one of them to growth over the other attaining final axonal identity.
These polarizing cues, include contact-mediated or secreted molecules acting over the fated axon. It is clear that individual polarity cues can function activating a plethora of various events including the differential expression of receptors and protein complexes, the selective accumulation of polarity regulators and cross talk between intracellular signaling cascades, at the growth cone of the fated axon.
Of these instructive cues, we currently study the role of neurotrophins (BDNF; NGF; NT-3) in axonal specification. Although there is considerable indication for the role of neurotrophins in neuronal polarity, the precise molecular mechanisms that underlie neurotrophin signal transduction in axonal specification remain unresolved.
Zuccaro E, Bergami M, Vignoli B, Bony G, Pierchala BA, Santi S, Cancedda L, Canossa M. 2014 Polarized expression of p75(NTR) specifies axons during development and adult neurogenesis. Cell Rep. Apr 10;7(1):138-52
Role of astrocytes for consolidating recognition memory engrams
A major issue in synaptic plasticity is to be able to assess the influence of individual synaptic sites - pre-synaptic, post-synaptic neurons and peri-synaptic glia - in promoting synaptic strengthening. This influence is typically attained by transmitters/modulators along with their complex interactions with selected receptors, and is regulated by activity.
The secretion of these synaptic factors at a definite concentration and time; their localization at selected synaptic compartments for specific receptors interaction; and complex ligand-receptor activation that identify synergistic recycling mechanisms; are all processes needed to support the strength and duration of synaptic signaling. From all these activities, it is conceivable to understand which sequence of synaptic events is undertaken, and what complex changes underline synaptic strengthening.
Moreover, all of these activities could coordinately couple neurons into functional assemblages (engrams) for memory processing.
We currently study the role of astrocytes in consolidating memory engrams. In a recent publication, we clearly demonstrated that that persistent modification of the synaptic strength, as long-term potentiation (LTP), requires glial BDNF recycling; a sequence of synaptic event initiated by BDNF clearing and re-release by glia.
Functionally, glial proBDNF recycling is recruited for shifting synaptic potentiation in perirhinal cortex from a short to a long-lasting form, thereby consolidating recognition memory (Vignoli et al., 2016). In spite of this clear functional relevance, why cortical glial cells are invited for neurotrophin recycling remains neglected and the significance of this cellular and molecular event in synaptic potentiation and memory consolidation is so far purely speculative.
Vignoli B, Battistini G, Melani R, Blum R, Santi S, Berardi N, Canossa M. 2016 Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention. Neuron. Nov 23;92(4):873-887