Pre- and postsynaptic properties of glutamatergic transmission in the immature inhibitory MNTB-LSO pathway

Abstract

The lateral superior olive (LSO) integrates excitatory inputs driven by sound arriving at the ipsilateral ear with inhibitory inputs driven by sound arriving at the contralateral ear in order to compute interaural intensity differences needed for localizing high-frequency sound sources. Specific mechanisms necessary for developmental refinement of the inhibitory projection, which arises from the medial nucleus of the trapezoid body (MNTB), have only been partially deciphered. The demonstration that immature MNTB-LSO synapses release glutamate has led to a model in which early glutamate neurotransmission plays a major role in inhibitory plasticity. We used whole cell electrophysiology in acute auditory brain stem slices of neonatal rats to examine glutamatergic transmission in the developing MNTB-LSO pathway. Unexpectedly, AMPA receptor (AMPAR)-mediated responses were prevalent at the earliest ages. We found a salient developmental profile for NMDA receptor (NMDAR) activation, described both by the proportion of total glutamate current and by current durations, and we found evidence for distinct release probabilities for GABA/glycine and glutamate in the MNTB-LSO pathway. The developmental profile of NMDAR is consistent with the possibility that the inhibitory MNTB-LSO pathway experiences a sensitive period, driven by cochlear activity and mediated by GluN2B-containing NMDARs, between postnatal days 3 and 9. Differing neurotransmitter release probabilities could allow the synapse to switch between GABA/glycinergic transmission and mixed glutamate/GABA/glycinergic transmission in response to changing patterns of spiking activity.

The Precise Temporal Pattern of Prehearing Spontaneous Activity Is Necessary for Tonotopic Map Refinement

“…In contrast, axonal pruning and sharpening occurs exclusively after hearing onset (Figure 6), when synaptic strengthening and silencing has already ceased (Walcher et al, 2011). The segregation of functional and structural refinement may indicate that functional and anatomical refinement each requires synaptic properties or activity patterns that are only present before or after hearing onset such as co-release glutamate or GABA from MNTB terminals (Case and Gillespie, 2011; Gillespie et al, 2005; Kotak et al, 1998; Nabekura et al, 2004, Noh et al, 2010) or an excitatory action of GABA/glycine (Kakazu et al, 1999; Kandler and Friauf, 1995; Kullmann et al, 2002). Linking these transient properties to specific processes in the functional and structural refinement of the MNTB-LSO pathway will be important for understanding tonotopic refinement auditory pathways and the developmental emergence of precise inhibitory circuits in other brain regions.…”

Synaptic Refinement of an Inhibitory Topographic Map in the Auditory Brainstem Requires Functional CaV1.3 Calcium Channels

“…Early in postnatal development, neurotransmission in the MNT-B-LSO synapses involves glutamate corelease (Gillespie et al, 2005;Case and Gillespie, 2011) which is crucially important for synapse refinement, suggesting that NMDA receptors play an important role in this process (Noh et al, 2010). As impaired NMDA receptor function may underlie the observed developmental defects in Ca V 1.3 Ϫ/Ϫ , we assessed whether NMDA receptor-mediated transmission from MNTB to LSO is changed in Ca V 1.3 Ϫ/Ϫ .…”

“…We cannot exclude the possibility that NMDA receptor mediated transmission is altered at a later stage of development. However, the glutamatergic component of the MNTB-LSO circuit declines after the first postnatal week (Case and Gillespie, 2011), implying that we examined NMDA receptor function within the time window in which it is most crucially needed for refinement of the MNTB-LSO circuit. Together, our results argue against the idea that impaired NMDA receptor function underlies the observed defects seen in Ca V 1.3 Ϫ/Ϫ .…”

Glycine receptors in nervous tissue and their functional role

“…Глицин (Gly) выполняет в организме целый ряд жизненно важных функций [1][2][3][4][5][6][7][8][9]. Он входит в состав многих белков и биологически активных соединений, из него синтезируются порфириновые кольца гема и пуриновые основания [10].…”

“…Данная аминокислота незаменима в регуляции нейромедиаторной синаптической трансмиссии в центральной и периферической нервной системе [1,7]. Рецепторы к Gly, локализованные во многих участках головного и спинного мозга, оказывают тормозное воздействие на нейроны, уменьшая выделение возбуждающих аминокислот [1][2][3]. В то же время глицин выступает в роли коагониста рецептора g-аминобутирата (GABA-R) и глутаматного рецептора NMDA-R [4][5][6][7][8].…”