Neural network activity in the neonatal rat barrel cortex in vivo

Coordinated patterns of electrical activity are important for the early development of sensory systems. The spatiotemporal dynamics of these early activity patterns and the role of the peripheral sensory input for their generation are essentially unknown. There are two projects in this thesis. In project1, we performed extracellular multielectrode recordings in the somatosensory cortex of postnatal day 0 to 7 rats in vivo and observed three distinct patterns of synchronized oscillatory activity. (1) Spontaneous and periphery-driven spindle bursts of 1–2 s in duration and ~10 Hz in frequency occurred approximately every 10 s. (2) Spontaneous and sensory-driven gamma oscillations of 150–300 ms duration and 30–40 Hz in frequency occurred every 10–30 s. (3) Long oscillations appeared only every ~20 min and revealed the largest amplitude (250–750 µV) and longest duration (>40 s). These three distinct patterns of early oscillatory activity differently synchronized the neonatal cortical network. Whereas spindle bursts and gamma oscillations did not propagate and synchronized a local neuronal network of 200–400 µm in diameter, long oscillations propagated with 25–30 µm/s and synchronized 600-800 µm large ensembles. All three activity patterns were triggered by sensory activation. Single electrical stimulation of the whisker pad or tactile whisker activation elicited neocortical spindle bursts and gamma activity. Long oscillations could be only evoked by repetitive sensory stimulation. The neonatal oscillatory patterns in vivo depended on NMDAreceptor-mediated synaptic transmission and gap junctional coupling. Whereas spindle bursts and gamma oscillations may represent an early functional columnar-like pattern, long oscillations may serve as a propagating activation signal consolidating these immature neuronal networks. In project2, Using voltage-sensitive dye imaging and simultaneous multi-channel extracellular recordings in the barrel cortex and somatosensory thalamus of newborn rats in vivo, we found that spontaneous and whisker stimulation induced activity patterns were restricted to functional cortical columns already at the day of birth. Spontaneous and stimulus evoked cortical activity consisted of gamma oscillations followed by spindle bursts. Spontaneous events were mainly generated in the thalamus or by spontaneous whisker movements. Our findings indicate that during early developmental stages cortical networks self-organize in ontogenetic columns via spontaneous gamma oscillations triggered by the thalamus or sensory periphery.

Neural network activity in the neonatal acute slice, slice culture and cell culture

Information processing and storage in the brain may be presented by the oscillations and cell assemblies. Here we address the question of how individual neurons associate together to assemble neural networks and present spontaneous electrical activity. Therefore, we dissected the neonatal brain at three different levels: acute 1-mm thick brain slice, cultured organotypic 350-µm thick brain slice and dissociated neuronal cultures. The spatio-temporal properties of neural activity were investigated by using a 60-channel Micro-electrode arrays (MEA), and the cell assemblies were studied by using a template-matching method. We find local on-propagating as well as large- scale propagating spontaneous oscillatory activity in acute slices, spontaneous network activity characterized by synchronized burst discharges in organotypic cultured slices, and autonomous bursting behaviour in dissociated neuronal cultures. Furthermore, repetitive spike patterns emerge after one week of dissociated neuronal culture and dramatically increase their numbers as well as their complexity and occurrence in the second week. Our data indicate that neurons can self-organize themselves, assembly to a neural network, present spontaneous oscillations, and emerge spatio-temporal activation patterns. The spontaneous oscillations and repetitive spike patterns may serve fundamental functions for information processing and storage in the brain.

Long-term potentiation and neural network activity in the neonatal rat cerebral cortex in vivo

Long-term potentiation in the neonatal rat rnbarrel cortex in vivo rnLong-term potentiation (LTP) is important for the activity-dependent formation of early cortical circuits. In the neonatal rodent barrel cortex LTP has been so far only studied in vitro. I combined voltage-sensitive dye imaging with extracellular multi-electrode recordings to study whisker stimulation-induced LTP for both the slope of field potential and the number of multi-unit activity in the whisker-to-barrel cortex pathway of the neonatal rat barrel cortex in vivo. Single whisker stimulation at 2 Hz for 10 min induced an age-dependent expression of LTP in postnatal day (P) 0 to P14 rats with the strongest expression of LTP at P3-P5. The magnitude of LTP was largest in the stimulated barrel-related column, smaller in the surrounding septal region and no LTP could be observed in the neighboring barrel. Current source density analyses revealed an LTP-associated increase of synaptic current sinks in layer IV / lower layer II/III at P3-P5 and in the cortical plate / upper layer V at P0-P1. This study demonstrates for the first time an age-dependent and spatially confined LTP in the barrel cortex of the newborn rat in vivo. These activity-dependent modifications during the critical period may play an important role in the development and refinement of the topographic map in the barrel cortex. (An et al., 2012)rnEarly motor activity triggered by gamma and spindle bursts in neonatal rat motor cortexrnSelf-generated neuronal activity generated in subcortical regions drives early spontaneous motor activity, which is a hallmark of the developing sensorimotor system. However, the neuronal activity patterns and functions of neonatal primary motor cortex (M1) in the early movements are still unknown. I combined voltage-sensitive dye imaging with simultaneous extracellular multi-electrode recordings in the neonatal rat S1 and M1 in vivo. At P3-P5, gamma and spindle bursts observed in M1 could trigger early paw movements. Furthermore, the paw movements could be also elicited by the focal electrical stimulation of M1 at layer V. Local inactivation of M1 could significantly attenuate paw movements, suggesting that the neonatal M1 operates in motor mode. In contrast, the neonatal M1 can also operate in sensory mode. Early spontaneous movements and sensory stimulations of paw trigger gamma and spindle bursts in M1. Blockade of peripheral sensory input from the paw completely abolished sensory evoked gamma and spindle bursts. Moreover, both sensory evoked and spontaneously occurring gamma and spindle bursts mediated interactions between S1 and M1. Accordingly, local inactivation of the S1 profoundly reduced paw stimulation-induced and spontaneously occurring gamma and spindle bursts in M1, indicating that S1 plays a critical role in generation of the activity patterns in M1. This study proposes that both self-generated and sensory evoked gamma and spindle bursts in M1 may contribute to the refinement and maturation of corticospinal and sensorimotor networks required for sensorimotor coordination.rn