Cycle 2 project 5

Project 5: Specificity and plasticity of lateral connections onto the dendritic tree of layer 2/3 pyramidal neurons in mouse visual cortex


PhD student: Patricia Molina-Luna, Venezuela
Home Institute:
Neuroscience Center Zürich; Principle Investigator: Björn Kampa
Host Institute: Amsterdam Neuroscience; Principle Investigator: Huibert Mansvelder

Executive Summary
Neurons in the visual cortex respond well to bars of different orientations moving into different directions. While this has been known for many decades and the underlying mechanisms of orientation and direction selectivity have been intensively studied, it is still unclear how we encode our natural visual environment. Each neuron in the visual cortex has a classical receptive field (CRF) like a keyhole through which it looks at the scenery in front of our eyes. Surround information from the non-classical receptive field (nCRF) fails to induce neuronal firing but can modulate the neuronal responses to their CRF stimulation. Recent studies have shown that natural movie stimulation beyond the CRF reduces the neuronal responses and concentrates them to brief   events (Vinje 2000 Science).

Furthermore, repeated stimulation with natural movies increases the reliability of single cell responses, which is again focused on brief response events (Yao 2007 Nat Neurosci). The reason for the increase in response reliability is thought be an increase in synaptic   strength which has been triggered by spike-timing dependent plasticity (STDP) mechanisms. Also, the coupling of bottom-up CRF inputs with top-down feedback from the surrounding nCRF can induce dendritic spikes which are large depolarizations in the dendrite and cause the cells to fire bursts of action potentials (Larkum 1999). These dendritic spikes have been shown in many cell types among them pyramidal neurons in layers 2/3 and 5 and they are also required for STDP induction (Kampa 2006 JPhysiol; Kampa 2007 TINS).

Hence, our hypothesis of the underlying mechanism for rapid learning in cortical coding of visual scenes is a coincidence detection of CRF inputs with correlated nCRF inputs from lateral connections across layer 2/3 inducing dendritic spikes and synaptic potentiation. We will use state-of the art electrophysiological and imaging techniques to investigate this hypothesis and to tackle the question how information about our visual environment is combined into a percept. Finally, we will modulate the changes in synaptic strength by activating the cholinergic pathway from the nucleus basalis which has been shown to increase reliability of cortical responses to natural movies (Goard 2010 Nat Neurosci). Contrarily, A recent study in the marmoset visual cortex has reported that acetylcholine reduces the effect of lateral connections by boosting the efficacy of thalamocortical connections via a nicotinic mechanism (Roberts 2005 JNeurophys). We will test the effect of nucleus basalis stimulation on response reliability and on response modulation by nCRF stimulation. Together, this study will shine light on important mechanisms of sensory integration and help to better understand how neuronal circuits are formed and function.

The PhD candidate for the proposed project is Ms Patricia Molina-Luna. She has successfully applied for a PhD Neuroscience Center of Zurich (ZNZ) and has started in my group in May 2010. She is currently practicing the preparation and we have successfully obtained the first electrophysiological recordings of visual cortex responses to natural movies.

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