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La Rosa, C.

Publications and source records attributed to La Rosa, C..

3 recordsLinked to original sources

Phylogenetic variation of immature neurons in mammalian amygdala: high prevalence in primate expanded nuclei projecting to neocortex

Structural changes involving new neurons can occur through stem cell-driven neurogenesis and late-maturing "immature" neurons, namely undifferentiated neuronal precursors frozen in a state of arrested maturation. The latter exist in the cerebral cortex, being particularly abundant in large-brained mammals. Similar cells have been described in the amygdala of some species, although their interspecies variation remain poorly understood. Here, their occurrence, number, molecular expression, and morphology were systematically analyzed in eight diverse mammalian species widely differing in neuroanatomy, brain size, lifespan, and socioecology. We show remarkable phylogenetic variation of the immature neurons in the amygdala, with a significantly greater prevalence in primates. The cells are associated with the amygdalas basolateral complex that in evolution has expanded in primates in conjunction with cortical projections, thus mimicking the general trend of the neocortex. These results support the emerging view that large brains performing complex socio-cognitive functions rely on wide reservoirs of immature neurons.

neuroscience↗

Developmental encoding of ultrasound vocalizations in the mouse auditory cortex

Mice communicate through high-frequency ultrasound vocalizations (USVs), which are crucial for social interactions such as courtship and aggression. Although USV representation has been found in adult brain areas along the auditory pathway, including the auditory cortex (ACx), no evidence is available on the neuronal representation of USVs early in life. Using in vivo two-photon calcium imaging, we analyzed ACx layer 2/3 neuronal responses to USVs, pure tones (4-90 kHz), and high-frequency modulated sweeps from postnatal day 12 (P12) to P21. We found that ACx neurons are tuned to respond to USV syllables as early as P12-P13, with an increasing number of responsive cells as the mouse age. By P14, while pure tone responses showed a frequency preference, no syllable preference was observed. Additionally, at P14, USVs, pure tones, and modulated sweeps activate clusters of largely non-overlapping responsive neurons. Finally, we show that while cell correlation decreases with increasing processing of peripheral auditory stimuli, neurons responding to the same stimulus maintain highly correlated spontaneous activity after circuits have attained mature organization, forming neuronal sub-networks sharing similar functional properties.

neuroscience↗

The role of alpha-helix on the structure-targeting drug design of amyloidogenic proteins

The most accredited hypothesis links the toxicity of amyloid proteins to their harmful effects on membrane integrity through the formation of prefibrillar-transient oligomers able to disrupt cell membranes. However, damage mechanisms necessarily assume a first step in which the amyloidogenic protein transfers from the aqueous phase to the membrane hydrophobic core. This determinant step is still poorly understood. However, according to our lipid-chaperon hypothesis, free lipids in solution play a crucial role in facilitating this footfall. Free phospholipid concentration in the aqueous phase acts as a switch between ion channel-like pore and fibril formation, so that high free lipid concentration in solution promotes pore and repress fibril formation. Conversely, low free lipids in the solution favor fibril and repress pore formation. This behavior is due to the formation of stable lipid-protein complexes. Here, we hypothesize that the helix propensity is a fundamental requirement to fulfill the lipid-chaperon model. The alpha-helix region seems to be responsible for the binding with amphiphilic molecules fostering the proposed mechanism. Indeed, our results show the dependency of protein-lipid binding from the helical structure presence. When the helix content is substantially lower than the wild type, the contact probability decreases. Instead, if the helix is broadening, the contact probability increases. Our findings open a new perspective for in silico screening of secondary structure-targeting drugs of amyloidogenic proteins.

biophysics↗