Sistemas Neuronais

Interesse da Investigação

We are interested in understanding the principles underlying the complex adaptive behavior of organisms. Starting with quantitative observations of animal behavior, we aim to integrate quantitative cellular and systems level experimental analysis of underlying neural mechanisms with theoretical, ecological and evolutionary contexts. Rats and mice provide flexible animal models that allow us monitor and manipulate neural circuits using electrophysiological, optical and molecular techniques. We have made progress using highly-controlled studies of a simple learned odor-cued decision task and are extending our focus toward more complex behaviors. Projects in the lab are wide-ranging and continually evolving. Current topics include (i) olfactory sensory decision-making, (ii) the function of the serotonin system, (iii) the role of uncertainty in brain function and behavior, (iv) role of frontal cortex in action inhibition.

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Membros do Grupo

Eric Dewitt	Postdoc
	Tel: 21 446 4680
Masayoshi Murakami	Postdoc
	Tel: 21 446 4680
Hope Johnson	Postdoc
	Tel: 21 446 4540
Magor Lorincz	Postdoc
	Tel: 21 446 4680
Gil Costa	External Ph.D. Student
	Tel: 21 446 4673
Sara Matias	External Ph.D. Student
	Tel: 21 446 4612
Niccolò Bonacchi	External Ph.D. Student
	Tel: 21 446 4682
Tatiana Vassilevskaia	Research Technician
	Tel: 21 446 4611
Leo Madruga	Research Technician
	Tel: 21 446 4540
Alexandra Piedade	Administrative Personnel
	Tel: 21 446 4682
Raquel Gonçalves	Administrative Personnel
	Tel: 21 446 4540
Patrícia Correia	2007 PGCN PhD Student
	Tel: 21 446 4514
Maria Inês Vicente	2007 PGCN PhD Student
	Tel: 21 446 4514
Ana Rita Fonseca	2008 PGCN PhD Student
	Tel: 21 446 4682
André Mendonça	2008 PGCN PhD Student
	Tel: 21 446 4680

Projecto de Investigação

Optogenetic identification and control of serotonin neurons in behaving animals

Serotonin is an important neurotransmitter implicated in a wide variety of physiological functions and pathophysiologies but whose function is not well understood. Critically, very little is known about the activity of serotonin-releasing neurons in the brain. This problem is greatly exacerbated by the difficulty in their identification during physiological recordings. To address these problems we are using a combination of behavioral analysis, electrophysiological recording and optical-genetic probes targeted through specific promoters to this class of cells. By selectively activating serotonin neurons with light delivered through implanted fiber optics, we will be able to positively identify them during recordings and to specifically activate them, allowing us to test specific hypotheses concerning the role of serotonin in brain function and behavior.

Funding

Marie Curie Intra-European Fellowship (IEF) #220098, awarded October 2008
Guillaume Dugué
Champalimaud Foundation

Colaboradores

Neuroethology Lab, Instituto Gulbenkian de Ciência
Susana Lima

Projecto de Investigação

Olfactory objects and decisions: From psychophysics to neural computation

Object recognition is an important and difficult problem solved by the nervous system. Although visual recognition is far more familiar to us, it is through the chemical senses that object recognition occurs for most organisms. Neural computations within the olfactory system enable faithful recognition and tracking of meaningful odor sources, even when they comprise complex chemical blends embedded in a sea of background odors. The overall aim of this line of work is to understand the neural computations that make olfactory object recognition possible. According to theoretical accounts, object recognition can be understood as a process of probabilistic inference. Under this hypothesis, complex odor stimuli are represented using a probabilistic population code and processed in a Bayesian optimal fashion by the nervous system. To link these normative ideas to specific neurophysiological and behavioral predictions, we are formalizing them using computational models. Experimentally, our main goal is to monitor and perturb object representations in the functioning, computing brain. To this end, we deploy psychophysical tasks in rats which formalize complex real-world olfactory problems and also allow us to operationalize cognitive processes such as attention and memory. By combining such quantitative paradigms with large-scale neural ensemble recordings in the olfactory cortex, we can study how populations of neurons encode and process complex odor scenes, attempt to account for behavioral performance, and test the predictions of theoretical models. At the level of neural circuits and their physiology, we are particularly interested in the origin of neuronal variability, the nature of inter-neuronal correlations, the properties of inter-areal brain communication and the action of neuromodulators.

Funding

Champalimaud Foundation

Colaboradores

University of Rochester, Rochester, New York, USA
Alex Pouget

Projecto de Investigação

Evaluating the reliability of knowledge: Neural mechanisms of confidence estimation

Humans and other animals must often make decisions on the basis of imperfect evidence. What is the neural basis for such judgments? How does the brain compute confidence estimates about predictions, memories and judgments? Previously, we found that a population of neurons in the orbitofrontal cortex (OFC) tracks the confidence in decision outcomes. We are seeking to extend these observations by testing whether confidence-related neural activity in the OFC is causally related to confidence judgments. We are also addressing how the uncertainty about a stimulus in the course of decision-making is computed in olfactory sensory cortex. These experiments will give us further insights into the nature of the neural processes underlying confidence estimation.

Funding

Champalimaud Foundation

Colaboradores

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA
Adam Kepecs

Projecto de Investigação

Frontal cortex and the control of impulsive action

Inhibition of behaviour is as important as its generation, and failure to inhibit inappropriate actions—impulsivity—is a central feature of pathologies including attention deficit hyperactivity disorder, drug addiction and obsessive compulsive disorder. Previous work has identified the frontal cortex as a central component in the control of inhibiting impulsive actions. The goal of this project is to understand how this brain area performs this function. Two current specific aims are to reveal the activity of frontal cortical neurons while rats are engaged in impulse control task and to examine the effect of inactivating subregions of frontal cortex on impulse control behavior. Recording from large ensembles of neurons in the medial prefrontal cortex (mPFC) and the secondary motor cortex (M2) of rats during performance of the impulse control task allows us to characterize in detail the neural activity in these areas in relationship to behavior. We find that the activity of subpopulations of mPFC and M2 neurons predict the impulse control performance of rats on a trial-by-trial basis. Preliminary results show that reversible inactivation of the mPFC also impairs the ability of rats to inhibit impulsive action. We are now seeking to understand in more detail the nature of the neural representations underlying impulse control.

Funding

Champalimaud Foundation

Publicações

Selected - updated October (2009).

Ranade SP, Mainen ZF. (2009). Transient firing of dorsal raphe neurons encodes diverse and specific sensory, motor and reward events. J Neurophysiol [Epub ahead of print] Link

Huber D, Petreanu L, Ghitani N, Ranade S, Hromádka T, Mainen Z, Svoboda K (2008). Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice Nature 451 :61-64

Kepecs A, Uchida N, Zariwala HA, Mainen ZF. (2008). Neural correlates, computation and behavioural impact of decision confidence. Nature 455(7210) :227-31 Link

Felsen G, Mainen ZF. (2008). Neural substrates of sensory-guided locomotor decisions in the rat superior colliculus. Neuron 60(1) :137-48 Link

Kepecs AC, Uchida N, Mainen ZF (2007). Rapid and precise control of sniffing during olfactory discrimination in rats J Neurophys 98 :205-13 Link

Uchida N, Mainen ZF. (2007). Odor concentration invariance by chemical ratio coding. Front Syst Neurosci 1 :3 Link

Wilson R, Mainen ZF (2006). Early events in olfactory processing Annu Rev Neurosci 29 :163-201 Link

Feierstein, Quirk , Uchida, Sosulski, Mainen ZF (2006). Representation of spatial goals in rat orbitofrontal cortex Neuron 51 :495-507 Link

Gurden, Uchida and Mainen ZF (2006). Sensory-evoked intrinsic optical signals in the olfactory bulb are coupled to glutamate release and uptake Neuron (Preview by Howarth and Attwell) 52 :335-345 Link

Uchida N., Mainen Z.F. (2003). Speed and accuracy of olfactory discrimination in the rat Nature Neurosci 6 :1224-1229 Link