Prof. Dr. Helmchen (CH)

Prof. Dr. Fritjof
Institut für Hirnforschung
Universität Zürich

 

Postnatal maturation of cortical microcircuit function
in
barrel cortex 

 

The neuronal microcircuits in the neocortex establish their function and fully mature during the first weeks of postnatal development. After birth the neocortex undergoes a series of developmental periods that are characterized by distinct patterns of intrinsic as well as sensory-evoked activity. While the formation of the essential synaptic connections, in particular during an experience-dependent critical period around P10-14 for rodent barrel cortex (Lendvai et al., 2000; Maravall et al., 2004b), has been recognized as one crucial aspect, the maturation of single-cell properties and of local microcircuit dynamics has been less well studied and therefore is poorly understood. In this subproject we aim to clarify how the intrinsic properties of individual neurons and the dynamics within microcircuits in the barrel cortex develop during the late phase of postnatal development, starting with the critical period and ending at the young adult stage (week 4-6) when cortex function has reached maturation. During this period we will directly measure single-cell properties such as input resistance, subthreshold membrane nonlinearities, and postsynaptic potentials as well as key features of the local network dynamics such as the density of action potential firing, the fraction of neurons responding during whisker activation, and the correlation structure within the network. We will study these aspects during spontaneous-ongoing activity, in response to whisker stimulation in the anesthetized animal, and – if possible - during active whisking in the awake animal, We will in particular compare the maturation of the excitatory and inhibitory neuronal subpopulations. Focusing on layer 2/3 neurons in mouse barrel cortex we will apply in vivo whole-cell recordings from identified excitatory or inhibitory neurons as well as novel two-photon microscopy techniques for network imaging that have been recently developed in our group.  For example, 3D laser scanning technology enables us to monitor activity patterns in several hundreds of cells within an identified barrel cortex column. Moreover, we have designed a high-speed two-photon microscope, with which we can reconstruct spike train patterns in a neuronal population with near-millisecond precision. Our hypothesis is that the maturation of the spatiotemporal activation patterns after the critical period is characterized by an overall reduction and sparsening of cortical activity, presumably reflecting fine-tuning and stabilization of signal processing chains. We aim to clarify in how far single-cell properties, such as reduced neuronal excitability, or network phenomena, such as increased inhibition or age-dependent changes in the neuromodulatory effects of the cholinergic input, may be responsible for such changes. Finally, in addition to monitoring the maturation of network dynamics under normal conditions we plan first experiments to examine how this development is affected by sensory deprivation ('whisker trimming') before and during the critical period. We expect that our experimental results regarding the postnatal maturation of barrel cortex function will help to identify key principles of cortical circuit dynamics.