scholarly journals Mechanisms Underlying Long-Term Synaptic Zinc Plasticity at Mouse Dorsal Cochlear Nucleus Glutamatergic Synapses

2020 ◽  
Vol 40 (26) ◽  
pp. 4981-4996 ◽  
Author(s):  
Nathan W. Vogler ◽  
Vincent M. Betti ◽  
Jacob M. Goldberg ◽  
Thanos Tzounopoulos
Keyword(s):  
Cochlear Nucleus ◽  
Dorsal Cochlear Nucleus ◽  
Glutamatergic Synapses

scholarly journals Single-neuron recordings from unanesthetized mouse dorsal cochlear nucleus

2012 ◽  
Vol 107 (3) ◽  
pp. 824-835 ◽  
Author(s):  
Wei-Li Diana Ma ◽  
Stephan D. Brenowitz
Keyword(s):  
Cochlear Nucleus ◽  
Single Neuron ◽  
Dorsal Cochlear Nucleus ◽  
Future Studies ◽  
Auditory Neuroscience ◽  
Neuronal Mechanisms ◽  
Auditory Physiology ◽  
Complex Spikes

Because of the availability of disease and genetic models, the mouse has become a valuable species for auditory neuroscience that will facilitate long-term goals of understanding neuronal mechanisms underlying the perception and processing of sounds. The goal of this study was to define the basic sound-evoked response properties of single neurons in the mouse dorsal cochlear nucleus (DCN). Neurons producing complex spikes were distinguished as cartwheel cells (CWCs), and other neurons were classified according to the response map scheme previously developed in DCN. Similar to observations in other rodent species, neurons of the mouse DCN exhibit relatively little sound-driven inhibition. As a result, type III was the most commonly observed response. Our findings are generally consistent with the model of DCN function that has been developed in the cat and the gerbil, suggesting that this in vivo mouse preparation will be a useful tool for future studies of auditory physiology.

scholarly journals Somatosensory context alters auditory responses in the cochlear nucleus

2011 ◽  
Vol 105 (3) ◽  
pp. 1063-1070 ◽  
Author(s):  
Patrick O. Kanold ◽  
Kevin A. Davis ◽  
Eric D. Young
Keyword(s):  
Auditory Processing ◽  
Cochlear Nucleus ◽  
Acoustic Stimulus ◽  
Electrical Stimulus ◽  
Dorsal Column ◽  
Dorsal Cochlear Nucleus ◽  
Initial Stimulus ◽  
Stimulus Pulse

The cochlear nucleus, the first central auditory structure, performs initial stimulus processing and segregation of information into parallel ascending pathways. It also receives nonauditory inputs. Here we show in vivo that responses of dorsal cochlear nucleus (DCN) principal neurons to sounds can change significantly depending on the presence or absence of inputs from the somatosensory dorsal column nucleus occurring before the onset of auditory stimuli. The effects range from short-term suppression of spikes lasting a few milliseconds at the onset of the stimulus to long-term increases or decreases in spike rate that last throughout the duration of an acoustic stimulus (up to several hundred milliseconds). The long-term effect requires only a single electrical stimulus pulse to initiate and seems to be similar to persistent activity reported in other parts of the brain. Among the DCN inhibitory interneurons, only the cartwheel cells show a long-term rate decrease that could account for the rate increases (but not the decreases) of DCN principal cells. Thus even at the earliest stages of auditory processing, the represented information is dependent on nonauditory context, in this case somatosensory events.

scholarly journals Bidirectional Long-Term Synaptic Zinc Plasticity at Mouse Glutamatergic Synapses

2018 ◽  
Author(s):  
Nathan W. Vogler ◽  
Thanos Tzounopoulos
Keyword(s):  
Low Frequency ◽  
Dorsal Cochlear Nucleus ◽  
High Frequency Stimulation ◽  
Glutamatergic Synapses ◽  
Zinc Signaling ◽  
Frequency Stimulation ◽  
Zinc Levels ◽  
Group 1

AbstractSynaptic zinc is coreleased with glutamate to modulate neurotransmission in many excitatory synapses. In the auditory cortex, synaptic zinc modulates sound frequency tuning and enhances frequency discrimination acuity. In auditory, visual, and somatosensory circuits, sensory experience causes long-term changes in synaptic zinc levels and/or signaling, termed here synaptic zinc plasticity. However, the mechanisms underlying synaptic zinc plasticity and the effects of this plasticity on long-term glutamatergic plasticity remain unknown. To study these mechanisms, we used male and female mice and employed in vitro and in vivo models in zinc-rich, glutamatergic dorsal cochlear nucleus (DCN) parallel fiber (PF) synapses. High-frequency stimulation of DCN PF synapses induced long-term depression of synaptic zinc signaling (Z-LTD), as evidenced by reduced zinc-mediated inhibition of AMPA receptor (AMPAR) excitatory postsynaptic currents (EPSCs). Low-frequency stimulation induced long-term potentiation of synaptic zinc signaling (Z-LTP), as evidenced by enhanced zinc-mediated inhibition of AMPAR EPSCs. Thus, Z-LTD is a new mechanism of LTP and Z-LTD is a new mechanism of LTP. Pharmacological inhibition of Group 1 metabotropic glutamate receptors (G1 mGluRs) eliminated Z-LTD and Z-LTP. Pharmacological activation of G1 mGluRs induced Z-LTD and Z-LTP, associated with bidirectional changes in presynaptic zinc levels. Finally, exposure of mice to loud sound caused G1 mGluR-dependent Z-LTD in DCN PF synapses, consistent with our in vitro results. Together, we show that G1 mGluR activation is necessary and sufficient for inducing bidirectional long-term synaptic zinc plasticity.Key points summarySynaptic zinc is coreleased with glutamate to modulate neurotransmission and auditory processing. Sensory experience causes long-term changes in synaptic zinc signaling, termed synaptic zinc plasticity.At zinc-containing glutamatergic synapses in the dorsal cochlear nucleus (DCN), we show that high-frequency stimulation reduces synaptic zinc signaling (Z-LTD), whereas low-frequency stimulation increases synaptic zinc signaling (Z-LTP).Group 1 metabotropic glutamate receptor (mGluR) activation is necessary and sufficient to induce Z-LTP and Z-LTD. Z-LTP and Z-LTD are associated with bidirectional changes in presynaptic zinc levels.Sound-induced Z-LTD at DCN synapses requires Group 1 mGluR activation.Bidirectional synaptic zinc plasticity is a previously unknown mechanism of LTP and LTD at zinc-containing glutamatergic synapses.

scholarly journals Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus

2017 ◽  
Vol 117 (3) ◽  
pp. 1229-1238 ◽  
Author(s):  
Roxana A. Stefanescu ◽  
Susan E. Shore
Keyword(s):  
Spontaneous Activity ◽  
Cochlear Nucleus ◽  
Acetylcholine Receptors ◽  
Dorsal Cochlear Nucleus ◽  
Muscarinic Acetylcholine Receptors ◽  
Fusiform Cell ◽  
Baseline Activity ◽  
Stimulus Timing

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N-methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology. NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology.

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