Bilaterally propagating waves of spontaneous activity arising from discrete pacemakers in the neonatal mouse cerebral cortex

Abstract

Spontaneous electrical activity that moves in synchronized waves across large populations of neurons plays widespread and important roles in nervous system development. The propagation patterns of such waves can encode the spatial location of neurons to their downstream targets and strengthen synaptic connections in coherent spatial patterns. Such waves can arise as an emergent property of mutually excitatory neural networks, or can be driven by a discrete pacemaker. In the mouse cerebral cortex, spontaneous synchronized activity occurs for approximately 72 h of development centered on the day of birth. It is not known whether this activity is driven by a discrete pacemaker or occurs as an emergent network property. Here we show that this activity propagates as a wave that is initiated at either of two homologous pacemakers in the temporal region, and then propagates rapidly across both sides of the brain. When these regions of origin are surgically isolated, waves do not occur. Therefore, this cortical spontaneous activity is a bilateral wave that originates from a discrete subset of pacemaker neurons.

Emergence of Adaptive Computation by Single Neurons in the Developing Cortex

“…In the neonatal mouse, waves of spontaneous activity are initiated in a discrete pacemaker region in the ventrolateral cortex (Lischalk et al, 2009) and propagate across the cortex from E17-P2 (Corlew et al, 2004;McCabe et al, 2006). Our results show that neurons at these early stages do not adjust excitability to compensate for the variance of input amplitudes.…”

“…Our results show that neurons at these early stages do not adjust excitability to compensate for the variance of input amplitudes. It is possible that this lower propensity for spontaneous firing, combined with higher intrinsic excitability in response to large inputs, may contribute to the ability of immature neurons to respond to pacemaker input by participating in spontaneous waves of activity, while at the same time avoiding asynchronous firing between waves of activity (Lischalk et al, 2009;Conhaim et al, 2010Conhaim et al, , 2011. In contrast, mature neurons responded to a wider range of stimuli (Fig.…”

Relationship between individual neuron and network spontaneous activity in developing mouse cortex

“…This difference as detected in wide-field imaging experiments is quantified in Figure 2D, a histogram of the ratio of the number of asynchronously active ventral cells to the number of asynchronously active dorsal cells per unit area in each experiment. This quantification shows that the number of cells with spontaneous activity between synchronous waves in ventral cortex was three times higher (36.9 Ϯ 5.6 cells·min Together, these data show that, in the pacemaker region of the piriform cortex, which initiates more than 99% of all spontaneous waves (Lischalk et al 2009), a larger fraction of cells show spontaneous calcium transients between waves than in the nonpacemaker dorsal cortex.…”

“…In the cerebral cortex, waves of SSA originate within a well-defined spatial region in the ventrolateral piriform cortex (Lischalk et al 2009), in contrast to other systems, such as the retina, in which activity initiates with equal probability throughout the structure (Meister et al 1991). In imaging experiments, 99% of observed synchronous activity in the cerebral cortex is initiated within this region.…”

“…In imaging experiments, 99% of observed synchronous activity in the cerebral cortex is initiated within this region. Moreover, when the region is surgically isolated from cortical slices, SSA continues to be generated within the isolated region, but SSA is eliminated in other parts of the cortex, suggesting that the ventrolateral piriform cortex is uniquely able to initiate SSA and can do so without input from other cortical regions (Lischalk et al 2009). In contrast, the dorsal neocortex does not initiate SSA.…”