Thesis Defense Seminar
Synapses are the fundamental nodes of information transmission in the brain. The efficacy of synaptic transmission, called synaptic strength and its use-dependent changes are crucial for how the brain perceives the environment, learns and stores memories. The highly diverse synaptic strengths found in a given connection at a particular moment in the hippocampal circuit may therefore reflect varied information coding and on-going learning associated with hippocampal-dependent tasks. However, the cellular and molecular basis by which synaptic strength diversity arises, that is, how synaptic strengths are set and controlled across a synapse population remain to be clarified. We have addressed this question by examining the interaction between multiple synapses of hippocampal neurons using a combination of electrophysiology and imaging approaches. We provide evidence for a novel cellular mechanism involving glial cells in regulating the heterogeneity of synaptic strengths across inputs received by single hippocampal neurons. Our findings underscore the role for glia in orchestrating synaptic transmission properties across a synapse population.
Understanding how social influence shapes biological processes is a central challenge in contemporary science, essential for achieving progress in a variety of fields ranging from the organization and evolution of coordinated collective action among neurons, or animals, to the dynamics of information exchange in human societies. Using an integrated experimental and theoretical approach I will address how, and why, animals exhibit highly-coordinated collective behavior, and what this can teach us about information processing more generally. I will demonstrate new imaging and immersive virtual reality technology that allows us to reconstruct (automatically) the dynamic, time-varying sensory networks by which social influence propagates in groups. This allows us to identify, for any instant in time, the most socially-influential individuals, and to predict the magnitude of complex behavioral cascades within groups before they actually occur. By investigating the coupling between spatial and information dynamics in groups we reveal that emergent problem solving is the predominant mechanism by which mobile groups sense, and respond to complex environmental gradients. I will also reveal the critical role uninformed, or unbiased, individuals play in effecting fast and democratic consensus decision-making in collectives, and will validate these predictions with experiments involving schooling fish and wild baboons. These results are shown to transcend specific systems, and may give new insights into how individual brains come to decisions, a hypothesis I will propose, and explore (preliminarily), with ongoing experiments of individual decision-making in immersive virtual environments.
The association cortices atrophy in cognitive disorders such as schizophrenia and Alzheimer’s Disease, while the primary visual cortex (V1) is more resilient. What makes the association cortices so vulnerable? We have been comparing the neurons that subserve visuo-spatial working memory in the primate dorsolateral prefrontal cortex (dlPFC), to neurons in V1 that respond to visual stimuli, and have found marked differences in both neurotransmission and modulation. Neurons in V1 show classic responses: they rely heavily on AMPAR neurotransmission, and cAMP signaling enhances neuronal firing, likely by increasing glutamate release. In contrast, dlPFC neurons have little reliance on AMPAR, and instead depend on cholinergic permissive effects on NMDAR transmission. These neurons are very dependent on arousal state, and feedforward, cAMP-calcium signaling increases K+ channel opening to reduce firing, e.g. during stress. Dysregulation of cAMP-calcium signaling with advancing age leads to loss of neuronal firing and impaired working memory, as well as tau phosphorylation. Dysregulated calcium-cAMP signaling and tau hyperphosphorylation are also seen in the aging entorhinal cortex, the cortical area most vulnerable in Alzheimer’s Disease. These data show how studies of the primate cortex can help to illuminate the etiology of cognitive disorders.
Thesis Defense Seminar
Animals rely on olfaction to find food, attract mates and avoid predators. In this talk I will present some of our recent findings about how different features of an odor stimulus, such as odor identity and odor intensity, are encoded in mouse piriform cortex, and will reveal the specific roles that different elements of the neural circuit play in shaping those representations.
Paola Arlotta is interested in understanding the molecular laws that govern the birth, differentiation, and assembly into working circuitry of clinically relevant neuron types in the cerebral cortex. The complexity of the nervous system fascinates her, and she is driven to integrate developmental and evolutionary knowledge to inform novel strategies for circuit repair in the cortex. Arlotta received her Master’s in Biochemistry from the University of Trieste, Italy, and her Ph.D. in Molecular Biology from the University of Portsmouth, UK. She came to Boston as a postdoctoral fellow in Neuroscience at Harvard Medical School and, in 2008, she joined the Harvard faculty. In 2014 she was promoted to Professor in the department of Stem Cell and Regenerative Biology and in 2018 she was appointed the inaugural professor to the Golub Family Chair. She has been a Principal Faculty Member at the Harvard Stem Cell Institute since 2007 and is also affiliated with the Center for Brain Science. Arlotta is the recipient of many awards, including the 2017 George Ledlie Prize from Harvard and a 2018 von Humboldt Foundation research award. Her work has been published in Science, Nature, Nature Neuroscience, Nature Cell Biology, and Neuron.
Thesis Defense Seminar
In humans, high visual acuity is restricted to a small (~1o) region of the retina: the foveola. Even if the foveola covers less than 1% of the visual field, the stimulus within this region can be complex, particularly when examining natural scenes. What are the contributions of attention and eye movements in foveal vision? Studying attention at this scale is challenging because small eye movements continuously shift the image on the retina, covering an area as large as the foveola itself. Furthermore, localizing the line of sight within a 1 degree region is challenging and beyond the capabilities of most eye-trackers. Thanks to a combination of techniques allowing for high-resolution recordings of eye position, retinal stabilization, and accurate gaze localization, we circumvented these challenges and examined how attention and visual exploration are controlled at the scale of the foveola. Here we show that fine spatial vision in the foveola is enhanced by means of three different mechanisms: (a) Covert shifts of attention. High-resolution attentional reallocations independent of eye movements improve vision at selected foveal locations. (b) Microsaccade preparation. Planning of microsaccades, saccades smaller than half a degree, enhances fine spatial vision at the microsaccade target location at the expenses of other nearby locations within the foveola. (c) Visual exploration. The visual system possesses not only a coarser priority map of the extrafoveal space to guide saccades, but also a finer grain priority map that is used to guide microsaccades once the region of interest is foveated. The precise repositioning of the preferred retinal locus by means of microsaccades enables visual exploration of foveal stimuli. Our findings show that, contrary to common intuition, simply placing a stimulus within the foveola is not sufficient for fine spatial vision; vision is the outcome of an orchestrated synergy of motor, cognitive and attentional factors at all levels, from the examination of visual scenes to the examination of detail.