Past events

As in many domains of cognition, the effects of context on memory are ubiquitous and pervasive. Even memory-impaired neurological patients and aging individuals with deficits in direct source recollection benefit from context reinstatement during retrieval. Though context effects on free and cued recall are robust, findings regarding context effects on recognition have been widely divergent. We have proposed a multifactorial model of context effects that takes into account the impact of hippocampally-based target-context binding, anterior medial temporal lobe-based additive familiarity, and frontal lobe-based strategic processes that suppress response bias to acheive mnemonic advantages. I will discuss findings from simulations and neuropsychological studies of the elderly that illustrate these factors. I will also present new data that suggest differences between temporal and spatial context and discuss their implications for memory models.

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.

The neurons of many basal ganglia nuclei, including the external and internal globus pallidus (GPe, GPi respectively) and the substantia nigra pars reticulta (SNr) are characterized by their high-frequency (50-100 spikes/s) tonic discharge (HFD). However, the high firing rate of GPe neurons is interrupted by long pauses. To provide insight into the GPe pause physiology, we developed an objective criterion for the quality of the isolation of extracellularly recorded spikes and studied the spiking activity of 212 well-isolated HFD GPe and 52 GPi/SNr neurons from five monkeys during different states of behavioral activity. An algorithm which maximizes the surprise function was used to detect pauses and pauser-cells ("pausers"). Only 6% of the GPi/SNr neurons vs. as many as 56% of the GPe neurons were classified as pausers. The average pause duration equals 0.6s and follows a Poissonian distribution with a frequency of 13 pauses/minute. No linear relation was found between pause parameters (duration or frequency) and the firing rate of the cell. Pauses were preceded by various changes in firing rate but not dominantly by a decrease. The average amplitude and duration of the spike waveform was modulated only after the pause but not before it. Pauses of pairs of cells which were recorded simultaneously were not correlated. The probability of GPe cells to pause spontaneously was extremely variable among monkeys (30-90%) and inversely related to the degree of the monkey's motor activity. These findings suggest that spontaneous GPe pauses are neither triggered by an intrinsic cellular mechanism nor by slow global changes in the extracellular medium and probably reflect a network property of the basal ganglia related to low-arousal and network exploration periods.