The neural mechanisms underlying learning and memory
have been proposed at the synaptic level and the network
level. Synaptic plasticity (such as long-term potentiation
and long-term depression) can be a way of encoding memory
information through long-lasting modification of the strength
of a specific set of synaptic connections. Coordinated
oscillatory activities in the neural network may provide
a spatial and temporal framework for the memory information
to be stored and transferred in different brain regions.
The hippocampus has been the prototypic model system for
the study of memory mechanisms.
The Ca2+/CaM-dependent protein phosphatase calcineurin
is suggested to be involved in certain types of synaptic
plasticity, such as LTD. But the exact role of calcineurin
in plasticity has been elusive due to the lack of cell-
type specific manipulation in previous studies. I have
generated a line of mice in which calcineurin gene is
specifically knocked out in the pyramidal neurons of the
CA1 region in the hippocampus. The role of calcineurin
in synaptic plasticity will be examined in the Schaffer
collateral Ð CA1 pathway where the gene is only missing
in the postsynaptic cells. The unique contribution of
CA1 plasticity to memory will also be assessed by behavioral
learning tasks and in vivo recording of CA1 place cell
activities in these mutant mice.
The inhibitory interneurons in the hippocampus have very
different properties from the excitatory principal neurons.
Although a minor population, ~10% of total neurons, they
are believed to play critical roles in shaping the activities
of excitatory neurons through feedforward and feedback
inhibition, and in generation of various rhythmic activities.
Due to their extreme anatomical and physiological diversities,
the functions carried out by interneurons are probably
also very diverse. Therefore it has been difficult to
study using conventional methods which lack cell-type
specificity. I am trying to develop interneuron subtype-specific
transgenic lines of mice. These lines will be used for
genetic manipulations in one type of interneurons at a
time, to dissect out interneurons' function in memory.
