Elsevier

Brain Research

Volume 1283, 4 August 2009, Pages 25-33
Brain Research

Research Report
Decline of long-term potentiation (LTP) in the rat auditory cortex in vivo during postnatal life: Involvement of NR2B subunits

https://doi.org/10.1016/j.brainres.2009.06.001Get rights and content

Abstract

A decline in the ability of synapses to express plasticity and long-term potentiation (LTP) during postnatal maturation has been characterized in primary visual and somatosensory cortices. The present study is the first to document changes in the magnitude of LTP in the primary auditory cortex (A1) of rats at different stages of postnatal life. In urethane-anesthetized rats, field postsynaptic potentials (fPSPs) in A1 were elicited by stimulation of the medial geniculate nucleus, and LTP of cortical fPSPs was induced by application of repeated episodes of theta burst stimulation. Rats tested between postnatal day (PD) 30–35 showed the greatest level of LTP, with fPSP amplitude reaching ∼ 165% of baseline after delivery of TBS. Levels of LTP decreased with increasing age, with ∼ 140% and ∼ 120% potentiation in rats aged PD 40–45 and 100–110, respectively. In rats older than 200 days, LTP could no longer be reliably induced (∼ 105–110% potentiation). Application of an antagonist of NMDA receptor NR2B subunits (Ro 25-6981, 10 mM) in A1 reduced LTP in PD 30–35 rats to levels similar to those in adults without affecting LTP in adults (PD 100–110). Additional pharmacological experiments demonstrated a critical role of AMPA, but not NMDA, receptors in eliciting baseline, non-potentiated fPSPs in A1, an effect not significantly influenced by age. Together, these experiments demonstrate a pronounced, age-related decline in plasticity of synapses in the rodent A1, with elevated levels of plasticity in juvenile animals requiring activation of NR2B subunits, known to facilitate plasticity in other cortical and subcortical circuits.

Introduction

Extensive evidence has shown that younger, immature brains are more plastic than the mature nervous system, due to the fact that the potential for re-organization of synaptic connectivity is at its peak during critical periods of early postnatal development (for reviews see Hensch, 2005, Dahmen and King, 2007, Daw et al., 2007, Keuroghlian and Knudsen, 2007). Reductions in plasticity with maturation are clearly evident in the visual system, as indicated by the decline in ocular dominance plasticity outside the critical period (Hubel and Wiesel, 1970, Daw et al., 1992, Lehmann and Löwel, 2008, Sato and Stryker, 2008) or the greater resistance to the induction of NMDA-dependent long-term potentiation (LTP) in the primary visual cortex (V1) of rodents with increasing age (Kato et al., 1991, Kirkwood et al., 1995, Jiang et al., 2007, Jang et al., 2009). Importantly, such age-related declines of LTP in V1 show marked differences among cortical layers, with thalamo-recipient layers (IV and deep III) showing little or no LTP at younger ages (after postnatal day 18 in mice), when supra- and infragranular layers still express substantial LTP in response to afferent stimulation (Wang and Daw, 2003, Jiang et al., 2007).

Results similar to those in V1 have also been obtained for plasticity and LTP measures in the rodent somatosensory cortex. Crair and Malenka (1995) found that LTP at thalamocortical synapses in the rat barrel cortex could only be induced prior to postnatal day (PD) 7. Interestingly, this time period corresponds to the critical period during which alterations in sensory input (e.g., lesioning of whisker follicles) effectively modify barrel cortex synaptic connectivity (Woolsey and Wann, 1976, Schlaggar et al., 1993), consistent with the hypothesis that LTP-like mechanisms mediate a variety of sensory-induced plasticity phenomena during early postnatal life (Feldman et al., 1999, Malenka and Bear, 2004).

Surprisingly, to the best of our knowledge, age-related changes in the induction and properties of LTP in the rodent primary auditory cortex (A1) have not been characterized. Like other sensory cortices, the synaptic and topographical structure (i.e., tonotopic organization) of A1 is influenced by the specific patterns of sensory input received during early postnatal life. For example, passive exposure to a tone of a specific frequency results in an enlargement of the cortical area in A1 responsive to that frequency if exposure occurs during a relatively tight sensitive period (PD 11–13 in rats; de Villers-Sidani et al., 2007). Further, significant changes in the expression of various NMDA receptor subunits (e.g., NR2A and NR2B) and GABAergic markers in A1 during postnatal development have been characterized (Hsieh et al., 2002, Bi et al., 2006, Kotak et al., 2008), factors known to impact the ability of synapses in other cortical areas to express LTP (Bear, 2003, Malenka and Bear, 2004). Consequently, the present experiments were designed to characterize LTP in the rat A1 in vivo from early adolescence to well into adulthood (> PD 200). In addition, the question of whether the NR2B subunit of the NMDA receptor plays a role in mediating some of the age-related differences in LTP was also addressed by means of local application of an NR2B subunit antagonist in A1.

Section snippets

Pharmacological characterization of fPSP elicited by MGN stimulation

The location of stimulation electrodes in the MGN and a typical placement of an electrode-dialysis probe assembly in A1 are shown in Fig. 1. Single pulse stimulation of the medial geniculate nucleus (MGN) in juvenile and adult rats (30–35 and 100–150 days, n = 5 and 7, respectively) under urethane anesthesia reliably elicited field postsynaptic potentials (fPSPs) recorded in the middle cortical layers (∼ 400–600 μm, layers IV–V) of A1. The fPSPs consisted of two, negative-going peaks, with

Discussion

Extensive evidence has shown that both age and sensory experience profoundly influence the ability of cortical synapses to undergo activity-dependent alterations in synaptic efficacy. Previous studies have demonstrated clear reductions in the ability of afferents to induce LTP in V1 and somatosensory cortex during early postnatal life, indicative of an increased resistance of cortical circuits to express changes in synaptic connectivity (Kato et al., 1991, Crair and Malenka, 1995, Kirkwood et

Animals

All subjects were treated in accordance with the regulations on animal experimentation established by the Canadian Council on Animal Care and the experimental procedures were approved by the Queen's University Animal Care Committee. Male Long–Evans rats of different ages (25, 35, or 70 days old) were obtained from Charles River (St. Constant, Quebec) and housed in a colony room until they were of appropriate age for experimentation (tested at PD 30–35, PD 40–45, PD 100–150, or PD + 200). All

Acknowledgments

The work described in the manuscript was funded by a grant from the National Sciences and Engineering Research Council of Canada (NSERC) to HCD. JLH is the recipient of a NSERC Graduate Scholarship.

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