NR2B subunit‐dependent long‐term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life

Abstract

The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

Chronic Fluoxetine Treatment Suppresses Plasticity (Long-Term Potentiation) in the Mature Rodent Primary Auditory CortexIn Vivo

“…), each rat was anesthetized with urethane to allow for the placement of a stimulating and recording electrode in the MGN and A1, respectively (Figure 2(a)). Consistent with previous wok [21, 22], extracellular recordings in the middle layers (III/IV) of A1 revealed that single pulse stimulation of the MGN elicited fPSPs consisting of two negative-going components with peak latencies of about 6–8 and 14–16 ms, respectively (Figure 2(b)). Previous work using current-source density analysis and pharmacological approaches has revealed that these two negative peaks correspond to current sinks associated with the sequential activation of direct, thalamocortical synapses (layer IV; first fPSP peak) and subsequent, intracortical synapses (layers II/III; second fPSP peak) [22, 24].…”

“…Consistent with previous wok [21, 22], extracellular recordings in the middle layers (III/IV) of A1 revealed that single pulse stimulation of the MGN elicited fPSPs consisting of two negative-going components with peak latencies of about 6–8 and 14–16 ms, respectively (Figure 2(b)). Previous work using current-source density analysis and pharmacological approaches has revealed that these two negative peaks correspond to current sinks associated with the sequential activation of direct, thalamocortical synapses (layer IV; first fPSP peak) and subsequent, intracortical synapses (layers II/III; second fPSP peak) [22, 24]. It is important to note that the urethane dose required for deep, surgical anesthesia did not differ significantly between the two groups of animals, with water and fluoxetine rats receiving a final dose of 2.12 ± 0.09 and 2.07 ± 0.06 g/kg of urethane, respectively (Figure 2(c)).…”

“…Electrophysiological assessments were carried out at the end of the treatment period (rat age of about 90–95 days) and followed previously established procedures [21, 22]. Rats were anesthetized using urethane (Sigma-Aldrich, Oakville, ON, Canada; 1.5 g/kg, given as three intraperitoneal (i.p.)…”

“…Stimulation trains were repeated every 10 s for a total of four trains. This induction protocol has previously been shown to elicit reliable LTP in the thalamocortical auditory system in vivo [21, 22]. After the TBS delivery, fPSPs were recorded for 60 min (every 30 s), followed by a second TBS episode (same as above) and a final 60 min of fPSP recordings.…”

NR2B subunit-specific NMDA antagonist Ro25-6981 inhibits the expression of conditioned fear

“…Local treatments in the amygdala and prefrontal cortex, that is, brain regions that are strongly involved in the emotional control and highly express the NR2B subunit, also impaired the acquisition of conditioned fear (Zhao et al, 2005;Cole andMcNally, 2008, Zhang et al, 2008). The NR2B, but not NR2A, subunit is also involved in NMDA-dependent alterations of a long-term potentiation (Gardoni et al, 2009;Hogsden and Dringenberg, 2009;Foster et al, 2010), a potential mechanism of trauma-induced behavioral dysfunctions (Adamec et al, 1999;Korol and Gold, 2008). Taken together, these findings strongly suggest that the NR2B subunit has an important role in mediating the role of NMDA receptors in trauma-induced behavioral dysfunctions.…”