Rapid Developmental Emergence of Stable Depolarization during Wakefulness by Inhibitory Balancing of Cortical Network Excitability

Abstract

The ability to generate behaviorally appropriate cortical network states is central to sensory perception and plasticity, but little is known about the timing and mechanisms of their development. I paired intracellular and extracellular recordings in the visual cortex of awake infant rats to determine the synaptic and circuit mechanisms regulating the development of a key network state, the persistent and stable subthreshold membrane potential (V m ) depolarization associated with wakefulness/alertness in cortical networks, called the "desynchronized" or "activated" state. Current-clamp recordings reveal that the desynchronized state is absent during the first 2 postnatal weeks, despite behavioral wakefulness. During this period, V m remains at the resting membrane potential Ͼ80% of the time, regardless of behavioral state. V m dynamics during spontaneous or light-evoked activity were highly variable, contained long-duration supratheshold plateau potentials, and high spike probability, suggesting an unstable and hyperexcitable early cortical network. Voltage-clamp recordings reveal that effective feedforward inhibition is absent at these early ages despite the presence of feedback inhibition. Stable membrane depolarization during wakefulness finally emerges 1-2 d before eye opening and is statistically indistinguishable from that in adults within days. Reduced cortical excitability, fast feedforward inhibition, and the slow cortical oscillation appear simultaneously with stable depolarization, suggesting that an absence of inhibitory balance during early development prevents the expression of the active state and hence a normal wakeful state in early cortex. These observations identify feedforward inhibition as a potential key regulator of cortical network activity development.

The Development of Nociceptive Network Activity in the Somatosensory Cortex of Freely Moving Rat Pups

“…In animals older than P13, this state is characterized by low-amplitude and high-frequency ECoG (Colonnese 2014). Epochs of 100 s were extracted from the continuous intracortical recordings.…”

Multisensory Intervention for Preterm Infants Improves Sucking Organization

“…This increased the frequency of alert states in premature infants 33-36 weeks PMA 7,6,25,26 and the frequency of orally directed behaviors. 5,27 The ATVV was administered after the baseline feeding assessment at 32 weeks PMA and twice daily for five days per week for 20 minutes prior to a morning and early afternoon feeding by the mother or research nurse. Mothers and research team members were trained in ATVV intervention and reliability (>90% agreement with the ATVV checklist) was established and maintained.…”

“…4 One of the challenges premature infants experience during the transiton to oral feeding is achieving and sustaining an alert behavioral state, such alertness being an indicator of appropriate behavioral organization. 5 Slight arousal prior to feeding helps infants achieve an active awake state, conducive to oral feeding. 6 Several oral and tactile sensory motor interventions have been suggested to support and enhance oral feeding, yet few if any have addressed how behavioral organization improves sucking behaviors.…”

Progressive Alignment of Inhibitory and Excitatory Delay May Drive a Rapid Developmental Switch in Cortical Network Dynamics

“…This 6-20Hz oscillation, the period of which is age-dependent, synchronize firing within the cortical column (Hanganu et al 2006;Shen and Colonnese 2016) and between cortex and thalamus Murata and Colonnese 2016). These oscillations disappear suddenly at the switch (P12) to be replaced by brief, graded responses to transient retinal activation, and persistent stable depolarization to extended activity Colonnese 2014). In vivo whole-cell recordings show that during the early stages periods of activity are unstable and the network does not produce an 'active' state, defined as a stable depolarized state, continuous during wakefulness, or alternating with down-states during sleep ( Fig.…”

“…The maturation of these early dynamics to adult-like networks occurs as a sudden transition in the network dynamics leading to an adult-like linear processing regime, asynchronous network activity and stable depolarization during activation. As measured in somatosensory and visual cortex, the synaptic changes most closely associated with this developmental switch are an increase in the amplitude of synaptic inhibition and a decrease in its delay (Minlebaev et al 2011;Colonnese 2014). It appears that through this process inhibition and excitation drive towards a general balance.…”