Neuroscience seminars

Courtship behavior is an innate model for many types of brain computations including sensory detection, learning and memory, and internal state modulation. Despite the robustness of the behavior, we have little understanding of the underlying neural circuits and mechanisms. The Stowers’ lab is leveraging the ability of specialized olfactory cues, pheromones, to specifically activate and therefore identify and study courtship circuits in the mouse. We are interested in identifying general circuit principles (specific brain nodes and information flow) that are common to all individuals, in order to additionally study how experience, gender, age, and internal state modulate and personalize behavior. We are solving two parallel sensory to motor courtship circuits, that promote social vocal calling and scent marking, to study information processing of behavior as a complete unit instead of restricting focus to a single brain region. We expect comparing and contrasting the coding logic of two courtship motor behaviors will begin to shed light on general principles of how the brain senses context, weighs experience and responds to internal state to ultimately decide appropriate action.

Neural stem cells reside in the adult mammalian brain. The ventricular-subventricular zone (V-SVZ) gives rise to olfactory bulb neurons, as well as small numbers of glia throughout life. Adult V-SVZ neural stem cells dynamically integrate intrinsic and extrinsic signals to either maintain the quiescent state or to become activated to divide and generate progeny. I will present our recent findings highlighting adult neural stem cell heterogeneity, including the identification of novel gliogenic domains and cell types, and the key roles of physiological state and long-range signals in the regulation of regionally distinct pools of adult neural stem cells.

n natural vision, active vision refers to the changes in visual input resulting from self-initiated eye movements. In this talk, I will present studies that show that the stimulus-related activity during active vision differs substantially from that occurring during classical flashed-stimuli paradigms. Our results uncover novel and efficient mechanisms that improve visual perception. In a general way, the nervous system appears to engage in sensory modulation mechanisms, precisely timed to self-initiated stimulus changes, thus coordinating neural activity across different cortical areas and serving as a general mechanism for the global coordination of visual perception.

Cognitive bias is a "subjective reality" that is uniquely created in the brain and affects our various behaviors. It may lead to what is widely called irrationality in behavioral economics, such as inaccurate judgment and illogical interpretation, but it also has an adaptive aspect in terms of mental hygiene. When such cognitive bias is regarded as a product of information processing in the brain, the approach to clarify the mechanism in the brain will play a part in finding the direct relations between the brain and the mind. In my talk, I will introduce our studies investigating the neural and molecular bases of cognitive biases, especially focusing on the role of dopamine.

The role of granule cells in olfactory processing is surrounded by several enigmatic observations, such as the existence of reciprocal spines and the mechanisms for GABA release from them, the missing evidence for functional reciprocal connectivity, and the apparently low inhibitory drive of granule cells, both with respect to recurrent and lateral inhibition. Here, I summarize recent results with regard to GABA release, leading to a novel hypothesis on granule cell function that has the potential to resolve most of these enigmas. I predict that granule cells provide dynamically switched lateral inhibition between coactive glomerular columns and thus possibly a means of olfactory combinatorial coding.

Many regions of the human brain conduct highly specific functions, such as recognizing faces, understanding language, and thinking about other people’s thoughts. Why might this domain specific organization be a good design strategy for brains, and what is the origin of domain specificity in the first place? In this talk, I will present recent work testing whether the segregation of face and object perception in human brains emerges naturally from an optimization for both tasks. We trained artificial neural networks on face and object recognition, and found that networks were able to perform both tasks well by spontaneously segregating them into distinct pathways. Critically, networks neither had prior knowledge nor any inductive bias about the tasks. Furthermore, networks optimized on tasks which apparently do not develop specialization in the human brain, such as food or cars, and object categorization showed less task segregation. These results suggest that functional segregation can spontaneously emerge without a task-specific bias, and that the domain-specific organization of the cortex may reflect a computational optimization for the real-world tasks humans solve.

The hippocampus lies at the centre of a network of brain regions thought to support spatial and episodic memory. Place cells - the principal cell of the hippocampus, represent information about an animal’s spatial location. Yet, during rest and awake quiescence place cells spontaneously recapitulate past trajectories (‘replay’). Replay has been hypothesised to support systems consolidation – the stabilisation of new memories via maturation of complementary cortical memory traces. Indeed, in recent work we found place and grid cells, from the deep medial entorhinal cortex (dMEC, the principal cortical output region of the hippocampus), replayed coherently during rest periods. Importantly, dMEC grid cells lagged place cells by ~11ms; suggesting the coordination may reflect consolidation. Moreover, preliminary data shows that the dMEC-hippocampal coordination strengthens as an animal becomes familiar with a task and that it may be led by directionally modulated cells. Finally, on-going work, in my recently established lab, shows replay may represent the mechanism underlying the maturation of episodic/spatial memory in pre-weanling pups. Together, these results indicate replay may play a central role in ensuring the permanency of memories.

Spontaneous behavior in animals and humans shows a striking amount of variability both in the spatial domain (which actions to choose) and temporal domain (when to act). Concatenating actions into sequences and behavioral plans reveals the existence of a hierarchy of timescales ranging from hundreds of milliseconds to minutes. How do multiple timescales emerge from neural circuit dynamics? How do circuits modulate temporal responses to flexibly adapt to changing demands? In this talk, we will present recent results from experiments and theory suggesting a new computational mechanism generating the temporal variability underlying naturalistic behavior. We will show how neural activity from premotor areas unfolds through temporal sequences of attractors, which predict the intention to act. These sequences naturally emerge from recurrent cortical networks, where correlated neural variability plays a crucial role in explaining the observed variability in action timing. We will then discuss how reaction times in these recurrent circuits can be accelerated or slowed down via gain modulation, induced by neuromodulation or perturbations. Finally, we will present a general mechanism producing a reservoir of multiple timescales in recurrent networks.

Adolescence is a period of life characterised by heightened sensitivity to social stimuli, an increased need for peer interaction and peer acceptance, and development of the social brain. Lockdown and social distancing measures intended to mitigate the spread of COVID-19 are reducing the opportunity to engage in face-to-face social interaction with peers. The consequences of social distancing on human social brain and social cognitive development are unknown, but animal research has shown that social deprivation and isolation have unique effects on brain and behaviour in adolescence compared with other stages of life. It is possible that social distancing might have a disproportionate effect on an age group for whom peer interaction is a vital aspect of development.

Rapid communication between the gut and the brain about recently consumed nutrients is critical for regulating food intake and maintaining energy homeostasis. We have shown that the infusion of nutrients directly into the gastrointestinal tract rapidly inhibits hunger-promoting AgRP neurons in the arcuate nucleus of the hypothalamus and suppresses subsequent feeding. The mechanism of this inhibition appears to be dependent upon macronutrient content, and can be recapitulated by a several hormones secreted in the gut in response to nutrient ingestion. In high-fat diet-induced obese mice, the response of AgRP neurons to nutrient-related stimuli are broadly attenuated. This attenuation is largely irreversible following weight loss and may represent a mechanism underlying difficulty with weight loss and propensity for weight regain in obesity.

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. To address these questions, we used a combination of extracellular recordings, neuronal decoding approaches, and optogenetic manipulations to show that threat representations and the initiation of avoidance behaviour are dynamically encoded in the overall population activity of dmPFC neurons. These data indicate that although dmPFC population activity at stimulus onset encodes sustained threat representations and discriminates threat- from non-threat cues, it does not predict action outcome. In contrast, transient dmPFC population activity prior to action initiation reliably predicts avoided from non-avoided trials. Accordingly, optogenetic inhibition of prefrontal activity critically constrained the selection of adaptive defensive responses in a time-dependent manner. These results reveal that the adaptive selection of active fear responses relies on a dynamic process of information linking threats with defensive actions unfolding within prefrontal networks.

Las enfermedades neurodegenerativas como la Enfermedad de Alzheimer, Enfermedad de Parkinson y la Esclerosis Lateral Amiotrófica tienen una prevalencia creciente en nuestra sociedad, de acuerdo con el aumento de la expectativa de vida. Durante el envejecimiento, las células gliales sufren cambios funcionales favoreciendo la “neuroinflamación”, que tiene un reconocido papel patogénico en la progresión de la enfermedad neurodegenerativa. Estudios recientes demuestran que durante el envejecimiento del sistema nervioso se acumulan notablemente células senescentes, tanto de estirpe neuronal como glial. Las células senescentes no proliferan, muchas de ellas exhiben un fenotipo secretor (SASP) con capacidad de inducir inflamación. La eliminación de células senescentes por ablación genética inducida farmacológicamente o por bloqueos de fármacos senolíticos mejoran la neuroinflamación y disminuyen la neurotoxicidad. En la presentación, se realizará una revisión de la bibliografía sobre este tema y se realizará un análisis del potencial terapéutico de fármacos senolíticos como una aproximación terapéutica novedosa de las enfermedades neurodegenerativas.