Donato Flavio, Chowdhury Ananya, Lahr Maria, Caroni Pico (2015), Early- and Late-Born Parvalbumin Basket Cell Subpopulations Exhibiting Distinct Regulation and Roles in Learning, in NEURON
, 85(4), 770-786.
Donato Flavio, Rompani Santiago Belluco, Caroni Pico (2013), Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning, in NATURE
, 504(7479), 272-272.
Caroni Pico, Chowdhury Ananya, Lahr Maria (2013), Synapse rearrangements upon learning: From divergent-sparse connectivity to dedicated sub-circuits, in Trends in Neurosciences
, 37(10), 604-614.
Ruediger Sarah, Spirig Dominique, Donato Flavio, Caroni Pico (2012), Goal-oriented searching mediated by ventral hippocampus early in trial-and-error learning, in NATURE NEUROSCIENCE
, 15(11), 1563-1571.
Caroni Pico, Donato Flavio, Muller Dominique (2012), Structural plasticity upon learning: Regulation and functions, in Nature Reviews Neuroscience
, 13(7), 478-490.
Structural plasticity modifies the connectivity of brain circuits by disassembling existing synapses and assembling new synaptic connections in response to experience. In spite of its major potential importance for learning, memory and resilience to dysfunction, this dramatic long-term form of plasticity has remained poorly understood. Structural plasticity may be particularly important in systems with prominent roles in learning and memory such as the hippocampus. The aim of our studies is to elucidate principles and mechanisms underlying structural plasticity of hippocampal circuits in the adult, and how that plasticity provides insights into hippocampal function. The projects are based on recent published findings from our lab, and address novel or unresolved issues of hippocampal function at the mechanistic level. They involve a broad spectrum of experimental approaches, but all rely on the analysis of identified neurons and synaptic structures, and aim at establishing causal relationships between modifications at those specific circuit elements, hippocampal function and mouse behavior.The following experimental approaches will represent the major effort of our laboratory over the next several years and are described in detail in this research plan:(1) Microcircuits of hippocampal principal neuron subpopulations: In these projects we will address the implications of our recent discovery of parallel principal neuron microcircuits with different structural plasticity properties in the hippocampus. We will investigate (1) the functional properties of the principal neuron subpopulations, (2) the mechanisms underlying their selective connectivity, and (3) their roles for information processing and learning in the hippocampus. (2) Circuit-specific control of developmental and adult plasticity in the hippocampus: In these projects we will investigate the mechanisms underlying parvalbumin (PV+) interneuron maturation in the hippocampus, a major target of control to regulate long-term plasticity in the juvenile and adult brain. We will investigate (1) circuit mechanisms underlying PV+ interneuron maturation in the hippocampus, (2) the role of temporal and spatial PV+ maturation patterns for hippocampal circuit assembly in juveniles, and (3) the possibility that similar mechanisms involving mossy fibers and PV+ neuron phenotypes may orchestrate plasticity in the adult.(3) Mechanisms regulating filopodial synapse numbers onto PV neurons in CA3: These projects build upon our discovery of filopodial synapses formation onto PV+ interneurons upon learning to investigate synaptogenesis mechanisms upon plasticity in the adult. We will investigate (1) the possible induction of filopodial synapses by ACh in vivo and in slice cultures, (2) the cellular regulation of LMT filopodial growth and synaptogenesis in slice cultures, and (3) the roles of feedforward inhibition connectivity levels for hippocampal learning and memory. (4) Hippocampal network plasticity in hippocampus-dependent learning: These projects exploit filopodial synapse increase upon learning in hippocampal CA3 as a sensitive readout for learning-related plasticity. The experiments aim at determining when and how the hippocampal network undergoes long-term plasticity related to learning, and at contrasting the roles of the hippocampus in memory, learning, and memory retrieval to support behavior. We will investigate (1) the roles of dorsal and ventral hippocampus in learning, and (2) the involvement of brain systems connected to the hippocampus in controlling hippocampal plasticity and learning.