Development of a barrel-related cortical column in the newborn rat
Zusammenfassung der Projektergebnisse
During the second BaCoFun funding period we characterized in more detail the properties of spontaneous and stimulus evoked network activity in newborn rodent barrel cortex and the mechanisms underlying the generation of spindle bursts (10-20 Hz) and gamma oscillations (30-40 Hz). We addressed these questions by using in vitro and in vivo imaging techniques, multi-site multi-electrode and patch-clamp recordings. The main results of our research during the second funding period can be summarized as follows: (1) Spontaneous and whisker stimulation-induced oscillatory activity synchronizes a local neocortical network into a functional ontogenetic column of 300-400 µm in diameter as early as postnatal day (P) 0 and the thalamus plays a central role in the transmission of this neocortical activity. At this early developmental stage a cortico-thalamic feedback loop modulates the spontaneously occurring and whisker stimulation-induced burst activity. (2) We propose a model that the central pattern generator (CGP) of the early cortical burst patterns is located in primary motor cortex (M1), brainstem and / or spinal cord. (3) We demonstrate that M1 is involved in somatosensory information processing already at neonatal stages and that M1 is mainly activated by tactile stimuli triggered by preceding spontaneous movements, which reach M1 via S1. Spontaneously occurring and sensory evoked gamma and spindle bursts in M1 may contribute to the maturation of corticospinal and sensorimotor networks required for the refinement of sensorimotor coordination. (4) Although GABAergic interneurons reveal subthreshold membrane resonance mediated by T-type Ca2+ and persistent Na+ currents, the low frequency of this resonance at ~2 Hz suggests that GABAergic interneurons probably do not play a major role in the generation of spindle bursts and gamma oscillations. (5) In cooperation with subproject 6 (Fritjof Helmchen) multi-electrode recordings and two-photon calcium imaging in anesthetized mice demonstrate that stimulus-evoked responses of neurons decreased in layers 2/3 (L2/3) and L4, but increased in L5 and L6. In addition to a progressive sparsification and decorrelation of neuronal activity, response selectivity for axial or lateral whisker movement emerged around the critical period. (6) Neuronal activity within the subplate (SP) is of critical importance for the development of neocortical circuits and architecture. Using in vitro patch-clamp recordings we demonstrate that ambient GABA contributes to regulate neuronal excitability in the SP. Non-synaptically released GABA tonically modulates excitatory GABAergic synaptic transmission. Since the GABA transporter GAT-1 operates in uptake mode and GAT-3 in reverse mode, balance of GAT activities can regulate the extracellular GABA concentration. Because of the immaturity of GABAergic synapses in the SP this inhibition mediated by presynaptic GABABRs on GABAergic synapses can modify early network oscillation.
Projektbezogene Publikationen (Auswahl)
- (2013) Barrel cortex function. Prog. Neurobiol. 103: 3-27
Feldmeyer, D., Brecht, M., Helmchen, F., Petersen, C.C., Poulet, J.F., Staiger, J.F., Luhmann, H.J., Schwarz, C.
(Siehe online unter https://doi.org/10.1016/j.pneurobio.2012.11.002) - (2013) Role of tonic GABAergic currents during preand early postnatal rodent development. Frontiers in Neural Circuits 7: 139
Kilb, W., Kirischuk, S. & Luhmann, H.J.
(Siehe online unter https://doi.org/10.3389/fncir.2013.00139) - (2013) Thalamic network oscillations synchronize ontogenetic columns in newborn rat barrel cortex. Cerebral Cortex 23: 1299-316
Yang, J.W., An, S., Sun, J.J., Reyes-Puerta, V., Kindler, J., Berger, T., Kilb, W. & Luhmann, H.J.
(Siehe online unter https://doi.org/10.1093/cercor/bhs103) - (2014) Early GABAergic circuitry in the cerebral cortex. Curr. Opin. Neurobiol. 26: 72-78
Luhmann, H.J., Kirischuk, S., Sinning, A., Kilb, W.
(Siehe online unter https://doi.org/10.1016/j.conb.2013.12.014) - (2014) Resonance properties of GABAergic interneurons in immature GAD67-GFP mouse neocortex. Brain Res. 1548: 1-11
Sun, H., An, S., Luhmann, H.J. & Kilb, W.
(Siehe online unter https://doi.org/10.1016/j.brainres.2013.12.032) - (2014) Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor cortex. J. Neuroscience 34:10870-83
An, S., Kilb, W., Luhmann, H.J.
(Siehe online unter https://doi.org/10.1523/JNEUROSCI.4539-13.2014) - (2014) Taurine activates GABAergic networks in the neocortex of immature mice. Frontiers Cellular Neuroscience 8: 26
Sava, B.A., Chen, R., Sun, H., Luhmann, H.J. & Kilb, B.
(Siehe online unter https://doi.org/10.3389/fncel.2014.00026) - (2015) GABA transporters control GABAergic neurotransmission in the mouse subplate. Neuroscience 304: 217-227
Unichenko P, Kirischuk S, Luhmann HJ
(Siehe online unter https://doi.org/10.1016/j.neuroscience.2015.07.067) - (2015) High stimulusrelated information in barrel cortex inhibitory interneurons. Plos Comput. Biology 11(6): e1004121
Reyes-Puerta V, Kim S, Sun JJ, Imbrosci B, Kilb W, Luhmann HJ
(Siehe online unter https://doi.org/10.1371/journal.pcbi.1004121) - (2015) Laminar and columnar structure of sensory-evoked multineuronal spike sequences in adult rat barrel cortex in vivo. Cerebral Cortex 25: 2001-2021
Reyes-Puerta, V., Sun, J.J., Kim, S., Kilb, W. Luhmann, H.J.
(Siehe online unter https://doi.org/10.1093/cercor/bhu007) - (2015) Long-range intralaminar noise correlations in the barrel cortex. J. Neurophysiol. 113(9):3410-3420
Reyes-Puerta V, Amitai Y, Sun JJ, Shani I, Luhmann HJ, Shamir M
(Siehe online unter https://doi.org/10.1152/jn.00981.2014) - (2015) Neocortical Layer 6B as a remnant of the subplate - a morphological comparison. Cerebral Cortex: 1-16
Marx M, Qi G, Hanganu-Opatz IL, Kilb W, Luhmann HJ, Feldmeyer D
(Siehe online unter https://doi.org/10.1093/cercor/bhv279) - (2016) Layer-specific refinement of sensory coding in developing mouse barrel cortex. Cerebral Cortex
van der Bourg A, Yang JW, Reyes-Puerta V, Laurenczy B, Wieckhorst M, Stüttgen MC, Luhmann HJ, Helmchen F
(Siehe online unter https://doi.org/10.1093/cercor/bhw280) - (2016) Spindle bursts in neonatal rat cerebral cortex. Neural Plasticity Epub 2016 Jan 13
Yang JW, Reyes-Puerta V, Kilb W, Luhmann HJ
(Siehe online unter https://doi.org/10.1155/2016/3467832) - (2016) Spontaneous neuronal activity in developing neocortical networks: from single cells to large-scale interactions. Frontiers in Neural Circuits 10: 40
Luhmann HJ, Sinning A, Yang JW, Reyes-Puerta V, Stüttgen MC, Kirischuk S, Kilb W
(Siehe online unter https://doi.org/10.3389/fncir.2016.00040)
