Down syndrome
Hippocampus and hippocampal network
Neurogenesis and environment
A first line of research is aimed at detecting the mechanisms
underlying brain hypotrophy in Down syndrome (DS), a genetic
disease characterized by severe mental retardation. In a transgenic
mouse model for DS (the Ts65Dn mouse) and brain samples from
fetuses with DS we are investigating alterations in the process of
neurogenesis in the subventricular zone (a region that contains the
progenitor of neurons that will populate the cerebral cortex), the
hippocampus and cerebellum, two structures notably hypotrophic in
DS patients. In the mouse model, we are trying to dissect the
molecular mechanisms underlying defective neuron formation in DS by
using in vivo and in vitro approaches. In an attempt to find
effective treatments, possibly useful in humans, we are also
focusing on therapies that could enhance neuron production.
A second line of research has the aim of obtaining insight into
the neuronal operations that take place in the hippocampal network,
with the hope to reveal the contribution of network activity to
memory functions. In particular, we are interested in the study of
signal transfer along the hippocampal-parahippocampal network, with
particular emphasis on the entorhinal cortex-hippocampus-entorhinal
cortex loop, a critically relevant circuit for learning and memory.
The research involves electrophysiological techniques in the
anesthetized guinea pig, with simultaneous multiple recordings of
extracellular field potentials and unit activity from the
hippocampal fields and entorhinal cortex and analysis of the
synaptic function (input-output function, current source density
profiles, short- and long- term plasticity) in each structure.
Different inputs and input patterns are used to reveal different
models of signal transfer, possibly related to different
behaviors.
A third line of research is aimed at investigating the long-term
effects of early life experiences on the organization of
hippocampal circuits essential for the establishment of long-term
memories. We investigate, in Guinea pig, the long term effects
of early life conditions on the hippocampal circuits with multiple
approaches involving electrophysiological, cellular biology and
morphometrical techniques. With this converging approaches we hope
to ascertain the impact of early life experiences on the synaptic
function of hippocampal networks and to identify structural plastic
changes (synapse formation, remodeling of dendrites, and
neurogenesis) and cellular mechanisms underlying the effects of
environment on the hippocampal function.
