Past events

An alternative model to the Declarative-Memory & Cognitive Map theories of the function of the hippocampus is suggested. the new model may explain the deficits described in the famous case of H.M., who displayed total anterograde amnesia following a surgery in which a bilateral dissection of the whole medial-temporal lobe (MTL) was perfromed (Scoville and Milner, 1957) . According to the model, the main functions of the MTL are: (1) to act as an integrator (2) to detect novelty. The integrator function is used, for example, for generation of the place-cell and grid-cell system. Normally, the MTL is integrating an episode until it detects a novel situation. Once the MTL detects such a novel situation, it sends the executive brain (perhaps the basal ganglia and/or prefrontal cortex) a message that it is time to play a novel behavioral game. In the case of H.M., where the MTL is missing, the executive brain never gets the message that an episode is novel, and thus continues to play "old games". In principle, at least, if this model is correct, H.M. could be cured from his memory problem, if the executive brain would have received the missing novelty signals artificially.

The mechanisms underlying our remarkable ability to form coherent and meaningful percepts in our complex environment are still an unresolved mystery. I propose that fast adaptive processes occurring at all levels of the processing hierarchy play a major role in this ability. I will give examples from speech perception and from tone comparison. A unique population in this respect are individuals with reading and learning disabilities. Their adaptive stimulus-specific mechanisms are impaired, with broad perceptual and cognitive consequences.

The mammalian brain maintains few developmental niches where neurogenesis persists into adulthood. One niche is located within the olfactory system where the olfactory bulb (OB) continuously receives newborn neurons that integrate into the network as functional interneurons. However, little is known about the mechanisms of development and function of this unique population. In this study, we set out to directly image newborn neurons and synapses by combining high resolution in vivo two-photon microscopy and lentivirus labeling. Overexpressing cytosolic GFP or a synaptic protein (PSD95-GFP) reveals the general dendritic structure and/or synaptic distributions along dendritic trees, respectively. In vivo imaging reveals the dynamic behavior of dendrites and synapses over time. Adult-born neurons were transduced at the subventricular zone and imaged in the OB where they start to mature into functional neurons. First, time-lapse imaging of newborn neurons over several days revealed that dendritic formation is highly dynamic with distinct dynamics for spiny neurons and non-spiny neurons. The dynamic nature of newborn development was not affected by sensory deprivation. Once incorporated into the network, adult-born neurons maintain significant levels of structural dynamics. This structural plasticity is local, cumulative and sustained in neurons several months after their integration. Second, synapse formation on these young cells and dendrites was verified by EM analysis of PSD95-GFP expressing cells. Using these neurons we found that early during development, synaptic distributions are highly ordered along dendritic trees. Third, these synapses continuously change locations along dendritic shafts as revealed time-lapse imaging over several days. Interestingly, these newborn neurons remain structurally dynamic months after they have been incorporated into the network. I will also discuss preliminary results where we use in vivo calcium to decipher the physiological activity of unique populations in the OB and cortex. These experiments provide an experimental model to directly study the dynamics of neuronal and synaptic development in the intact mammalian brain and provide direct evidence for the ongoing plasticity of the adult-born neuronal population.

The arrival times of a sound at the two ears are only microseconds apart, but both birds and mammals can use these interaural time differences to localize low-frequency sounds. Traditionally, it was thought that the underlying mechanism involved only coincidence detection of excitatory inputs from the two ears. However, recent findings have uncovered profound roles for synaptic inhibition in the processing of interaural time differences. In mammals, exquisitely timed hyperpolarizing inhibition adjusts the temporal sensitivity of coincidence detector neurons to the physiologically relevant range of interaural time differences. Inhibition onto bird coincidence detectors, by contrast, is depolarizing and devoid of temporal information, providing a mechanism for gain control.