Postnatal Differentiation of Basket Cells from Slow to Fast Signaling Devices

Abstract

Gamma frequency (30 -100 Hz) oscillations in the mature cortex underlie higher cognitive functions. Fast signaling in GABAergic interneuron networks plays a key role in the generation of these oscillations. During development of the rodent brain, gamma activity appears at the end of the first postnatal week, but frequency and synchrony reach adult levels only by the fourth week. However, the mechanisms underlying the maturation of gamma activity are unclear. Here we demonstrate that hippocampal basket cells (BCs), the proposed cellular substrate of gamma oscillations, undergo marked changes in their morphological, intrinsic, and synaptic properties between postnatal day 6 (P6) and P25. During maturation, action potential duration, propagation time, duration of the release period, and decay time constant of IPSCs decreases by ϳ30 -60%. Thus, postnatal development converts BCs from slow into fast signaling devices. Computational analysis reveals that BC networks with young intrinsic and synaptic properties as well as reduced connectivity generate oscillations with moderate coherence in the lower gamma frequency range. In contrast, BC networks with mature properties and increased connectivity generate highly coherent activity in the upper gamma frequency band. Thus, late postnatal maturation of BCs enhances coherence in neuronal networks and will thereby contribute to the development of cognitive brain functions.

Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?

“…In primates and rodents, the delay in achieving mature performance on executive function tasks correlates with the maturation of oscillatory activity in the gamma range and with the maturation of PV-interneuronal networks (Wilson et al, 1994;Rao et al, 2000;Doischer et al, 2008;Uhlhaas et al, 2009), consistent with the delayed maturation of PV-inhibitory circuits. Development of PV-synaptic contacts, which sculpt this inhibitory network throughout childhood and adolescence, is dependent on GAD67 synthesis and activity in rodents (Chattopadhyaya et al, 2007).…”

“…Profound changes in the ion-channel repertoire expressed at different time-points during the first postnatal month shape the electrophysiological maturation required to attain the characteristic fast-spiking non-accommodating current patterns observed in adulthood. Oscillatory activity in the gamma range also begins during this second postnatal week, and matures throughout the following weeks to reach adult levels by the end of the adolescent period (Doischer et al, 2008). In non-human primates, the appearance of parvalbumin expression and development of PV-synaptic contacts begins at around 3 months of age, and develops profusely throughout childhood and adolescence (Reynolds and Beasley 2001;Cruz et al, 2003).…”

“…These results suggest that PV-interneurons are more resistant to the effects of NMDA-R antagonists during the rodent equivalent to the adolescence period in humans. The overwhelming proliferation of PV-synaptic contacts observed before adolescence (Cruz et al, 2003), as well as the slow functional maturation of PV-inhibitory network (Doischer et al, 2008;Okaty et al, 2009) may explain the lack of pro-psychotic effects of NMDA-R antagonists before early adulthood. However, hormonal influences or changes in receptor-expression patterns (Okaty et al,.…”

Long-term sensory deprivation selectively rearranges functional inhibitory circuits in mouse barrel cortex

“…Changes in decay kinetics, even on the millisecond timescale, can alter the synchronization of large populations of neurons (53,54), particularly if fast decay from ␣1 subunits is involved (55). Thus, as our result of increased firing frequency in LTS cells shows, even subtle changes in recurrent inhibition onto LTS cells may result in significant consequences such as observed in basket cell development (56). The fact that this change occurs on LTS cells is especially significant.…”

Dissecting Neuronal Circuits: Analysis of Basket Cell-like Interneurons in Cortical Layer 6

“…Substantial changes in the intrinsic electrophysiological and synaptic properties, as well the morphologies, occur early in development, including for BCs (Doischer et al, 2008). However, these changes are most pronounced up to the third post-natal week (Doischer et al, 2008).…”