scholarly journals Glycinergic inhibition to the medial nucleus of the trapezoid body shows prominent facilitation and can sustain high levels of ongoing activity

2014 ◽  
Vol 112 (11) ◽  
pp. 2901-2915 ◽  
Author(s):  
Florian Mayer ◽  
Otto Albrecht ◽  
Anna Dondzillo ◽  
Achim Klug
Keyword(s):  
Meriones Unguiculatus ◽  
Inhibitory Synapses ◽  
Auditory Information ◽  
Activity Levels ◽  
Synaptic Currents ◽  
Medial Nucleus ◽  
Highly Active ◽  
Glycinergic Inhibition ◽  
Trapezoid Body

Neurons in the medial nucleus of the trapezoid body (MNTB) are well known for their prominent excitatory inputs, mediated by the calyx of Held. Less attention has been paid to the prominent inhibitory inputs that MNTB neurons also receive. Because of their auditory nature, both excitatory and inhibitory synapses are highly active in vivo. These high levels of activity are known to reduce excitatory synaptic currents considerably, such that in vivo synaptic currents produced by the calyx are smaller than typically measured in standard brain slice experiments. The goal of this study was to investigate the properties of the inhibitory inputs in the Mongolian gerbil ( Meriones unguiculatus) under activity levels that correspond to those in the intact brain to facilitate a direct comparison between the two inputs. Our results suggest that inhibitory inputs to MNTB are largely mediated by a fast and phasic glycinergic component, and to a lesser degree by a GABAergic component. The glycinergic component can sustain prolonged high levels of activity. Even when challenged with stimulus patterns consisting of thousands of stimuli over tens of minutes, glycinergic inputs to MNTB maintain large conductances and fast decays and even facilitate substantially when the stimulation frequency is increased. The inhibition is mediated by a relatively small number of independent input fibers. The data presented here suggest that inhibitory inputs to MNTB sustain high levels of activity and need to be considered for a full understanding of mechanisms underlying processing of auditory information in MNTB.

scholarly journals Functional Role of GABAergic and Glycinergic Inhibition in the Intermediate Nucleus of the Lateral Lemniscus of the Big Brown Bat

2009 ◽  
Vol 101 (6) ◽  
pp. 3135-3146 ◽  
Author(s):  
Andrew Kutscher ◽  
Ellen Covey
Keyword(s):  
Gain Control ◽  
Stimulus Onset ◽  
Auditory Information ◽  
Lateral Lemniscus ◽  
Intermediate Nucleus ◽  
Medial Nucleus ◽  
Big Brown Bat ◽  
Glycinergic Inhibition

The intermediate nucleus of the lateral lemniscus (INLL) is a major input to the inferior colliculus (IC), the auditory midbrain center where multiple pathways converge to create neurons selective for specific temporal features of sound. However, little is known about how INLL processes auditory information or how it contributes to integrative processes at the IC. INLL receives excitatory projections from the cochlear nucleus and inhibitory projections from the medial nucleus of the trapezoid body (MNTB), so it must perform some form of integration. To address the question of what role inhibitory synaptic inputs play in the INLL of the big brown bat ( Eptesicus fuscus), we recorded sound-evoked responses of single neurons and iontophoretically applied bicuculline to block GABAA receptors or strychnine to block glycine receptors. Neither bicuculline nor strychnine had a consistent effect on response latency or frequency response areas. Bicuculline increased spike counts and response durations in most units, suggesting that GABAergic input suppressed the late part of the response and provided some gain control. Strychnine reduced the responses of some units with sustained discharge patterns to one or a few spikes at stimulus onset, but increased others. INLL is the only part of the auditory system where reduced responsiveness has been seen in vivo while blocking glycine. However, in vitro studies in the MNTB suggest that glycine can be facilitatory, possibly through presynaptic action. These results show that GABA consistently reduces spike counts and response durations, whereas glycine is suppressive in some INLL neurons but facilitatory in others.

Extraction of Auditory Information by Modulation of Neuronal Ion Channels

2018 ◽  
pp. 272-300
Author(s):  
Leonard K. Kaczmarek
Keyword(s):  
Ion Channels ◽  
Neuronal Firing ◽  
Auditory Information ◽  
Auditory Neurons ◽  
Complex Sound ◽  
Medial Nucleus ◽  
Rapid Changes ◽  
Genes Encoding ◽  
Kinetics Of ◽  
Trapezoid Body

All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.

scholarly journals GABAB and Trk Receptor Signaling Mediates Long-Lasting Inhibitory Synaptic Depression

2001 ◽  
Vol 86 (1) ◽  
pp. 536-540 ◽  
Author(s):  
Vibhakar C. Kotak ◽  
Christopher DiMattina ◽  
Dan H. Sanes
Keyword(s):  
Synaptic Depression ◽  
Inhibitory Synapses ◽  
Receptor Signaling ◽  
Lateral Superior Olive ◽  
Superior Olive ◽  
Medial Nucleus ◽  
Dependent Form ◽  
Early Expression ◽  
Neurotrophin Signaling ◽  
Trapezoid Body

In many areas of the nervous system, excitatory and inhibitory synapses are reconfigured during early development. We have previously described the anatomical refinement of an inhibitory projection from the medial nucleus of the trapezoid body to the lateral superior olive in the developing gerbil auditory brain stem. Furthermore, these inhibitory synapses display an age-dependent form of long-lasting depression when activated at a low rate, suggesting that this process could support inhibitory synaptic refinement. Since the inhibitory synapses release both glycine and GABA during maturation, we tested whether GABAB receptor signaling could initiate the decrease in synaptic strength. When whole cell recordings were made from lateral superior olive neurons in a brain slice preparation, the long-lasting depression of medial nucleus of the trapezoid body–evoked inhibitory potentials was eliminated by the GABABreceptor antagonist, SCH-50911. In addition, inhibitory potentials could be depressed by repeated exposure to the GABAB receptor agonist, baclofen. Since GABAB receptor signaling may not account entirely for inhibitory synaptic depression, we examined the influence of neurotrophin signaling pathways located in the developing superior olive. Bath application of brain-derived neurotrophic factor or neurotrophin-3 depressed evoked inhibitory potentials, and use-dependent depression was blocked by the tyrosine kinase antagonist, K-252a. We suggest that early expression of GABAergic and neurotrophin signaling mediates inhibitory synaptic plasticity, and this mechanism may support the anatomical refinement of inhibitory connections.

scholarly journals GABAergic and glycinergic inhibition modulate monaural auditory response properties in the avian superior olivary nucleus

2011 ◽  
Vol 105 (5) ◽  
pp. 2405-2420 ◽  
Author(s):  
W. L. Coleman ◽  
M. J. Fischl ◽  
S. R. Weimann ◽  
R. M. Burger
Keyword(s):  
Phase Locking ◽  
Auditory Brainstem ◽  
Inhibitory Input ◽  
Auditory Information ◽  
Low Frequencies ◽  
Response Properties ◽  
Glycinergic Inhibition ◽  
Olivary Nucleus

The superior olivary nucleus (SON) is the primary source of inhibition in the avian auditory brainstem. While much is known about the role of inhibition at the SON's target nuclei, little is known about how the SON itself processes auditory information or how inhibition modulates these properties. Additionally, the synaptic physiology of inhibitory inputs within the SON has not been described. We investigated these questions using in vivo and in vitro electrophysiological techniques in combination with immunohistochemistry in the chicken, an organism for which the auditory brainstem has otherwise been well characterized. We provide a thorough characterization of monaural response properties in the SON and the influence of inhibitory input in shaping these features. We found that the SON contains a heterogeneous mixture of response patterns to acoustic stimulation and that in most neurons these responses are modulated by both GABAergic and glycinergic inhibitory inputs. Interestingly, many SON neurons tuned to low frequencies have robust phase-locking capability and the precision of this phase locking is enhanced by inhibitory inputs. On the synaptic level, we found that evoked and spontaneous inhibitory postsynaptic currents (IPSCs) within the SON are also mediated by both GABAergic and glycinergic inhibition in all neurons tested. Analysis of spontaneous IPSCs suggests that most SON cells receive a mixture of both purely GABAergic terminals, as well as terminals from which GABA and glycine are coreleased. Evidence for glycinergic signaling within the SON is a novel result that has important implications for understanding inhibitory function in the auditory brainstem.

Chronic NMDA Exposure Accelerates Development of GABAergic Inhibition in the Superior Colliculus

2000 ◽  
Vol 83 (3) ◽  
pp. 1580-1591 ◽  
Author(s):  
Sandra M. Aamodt ◽  
Jian Shi ◽  
Matthew T. Colonnese ◽  
Wellington Veras ◽  
Martha Constantine-Paton
Keyword(s):  
Superior Colliculus ◽  
Cell Voltage ◽  
Ethylene Vinyl Acetate ◽  
Cell Counting ◽  
Inhibitory Synapses ◽  
Synaptic Currents ◽  
Neuron Density ◽  
Visual Inputs ◽  
Cortical Inputs

Maturation of excitatory synaptic connections depends on the amount and pattern of their activity, and activity can affect development of inhibitory synapses as well. In the superficial visual layers of the superior colliculus (sSC), developmental increases in the effectiveness of γ-aminobutyric acid (GABAA) receptor–mediated inhibition may be driven by the maturation of visual inputs. In the rat sSC, GABAAreceptor currents significantly jump in amplitude between postnatal days 17 and 18( P17 and P18), approximately when the effects of cortical inputs are first detected in collicular neurons. We manipulated the development of these currents in vivo by implanting a drug-infused slice of the ethylene-vinyl acetate copolymer Elvax over the superior colliculus of P8 rats to chronically release from this plastic low levels of N-methyl-d-aspartate (NMDA). Sham-treated control animals received a similar implant containing only the solvent for NMDA. To examine the effects of this treatment on the development of GABA-mediated neurotransmission, we used whole cell voltage-clamp recording of spontaneous synaptic currents (sPSCs) from sSC neurons in untreated, NMDA-treated, and sham-treated superior colliculus slices ranging in age from 10 to 20 days postnatal. Both amplitude and frequency of sPSCs were studied at holding potentials of +50 mV in the presence and absence of the GABAA receptor antagonist, bicuculline methiodide (BMI). The normal developmental increase in GABAA receptor currents occurred on schedule ( P18) in sham-treated sSC, but NMDA treatment caused premature up-regulation ( P12). The average sPSCs in early NMDA-treated neurons were significantly larger than in age-matched sham controls or in age-matched, untreated neurons. No differences in average sPSC amplitudes across treatments or ages were present in BMI-insensitive, predominantly glutamatergic synaptic currents of the same neurons. NMDA treatment also significantly increased levels of glutamate decarboxylase (GAD), measured by quantitative western blotting with staining at P13 and P19. Cell counting using the dissector method for MAP 2 and GAD67 at P13 and P19indicated that the differences in GABAergic transmission were not due to increases in the proportion of inhibitory to excitatory neurons after NMDA treatment. However, chronic treatments begun at P8 with Elvax containing both NMDA and BMI significantly decreased total neuron density at P19 (∼15%), suggesting that the NMDA-induced increase in GABAA receptor currents may protect against excitotoxicity.

scholarly journals Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

2019 ◽  
Author(s):  
V. Korzhova ◽  
P. Marinković ◽  
P. M. Goltstein ◽  
J. Herms ◽  
S. Liebscher
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Amyloid Plaque ◽  
Activity Levels ◽  
Highly Active ◽  
Over Time

SummaryAlzheimer’s disease (AD) is associated with aberrant neuronal activity levels. How those activity alterations emerge and how stable they are over time in vivo, however, remains elusive to date. To address these questions we chronically recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice and their non-transgenic littermates over the course of 4 weeks by means of calcium imaging. Surprisingly, aberrant neuronal activity was very stable over time. Moreover, we identified a slow progressive gain of activity of former intermediately active neurons as the main source of new highly active neurons. Interestingly, fluctuations in neuronal activity were independent from amyloid plaque proximity, but aberrant activity levels were more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in AD patients is the consequence of stable single cell aberrant neuronal activity, a finding of potential therapeutic relevance.

scholarly journals Using cortical neuron markers to target cells in the dorsal cochlear nucleus

2020 ◽  
Author(s):  
Thawann Malfatti ◽  
Barbara Ciralli ◽  
Markus M. Hilscher ◽  
Steven J. Edwards ◽  
Klas Kullander ◽  
...  
Keyword(s):  
Cochlear Nucleus ◽  
Viral Vectors ◽  
Dorsal Cochlear Nucleus ◽  
Target Cells ◽  
Light Stimulation ◽  
Calcium Calmodulin Dependent ◽  
Medial Nucleus ◽  
Dependent Protein ◽  
Trapezoid Body

AbstractThe dorsal cochlear nucleus (DCN) is the first auditory region that integrates somatosensory and auditory inputs. The region is of particular interest for auditory research due to the large incidence of somatic tinnitus and increased aberrant activity in other forms of tinnitus. Yet, the lack of useful genetic markers for in vivo manipulations hinders the elucidation of the DCN contribution to tinnitus pathophysiology. In this work, we assessed whether adeno-associated viral vectors (AAV) containing the calcium/calmodulin-dependent protein kinase 2 alpha (CaMKIIα) promoter and our mouse line of nicotinic acetylcholine receptor alpha 2 subunit (Chrna2)-Cre can be used to target specific DCN populations. The CaMKIIα promoter is usually applied in studies of principal neurons of neo and paleocortex while Chrna2-cre mice express Cre recombinase in cortical dendrite inhibiting interneurons. We found that CaMKIIα cannot be used to specifically target excitatory fusiform DCN neurons. EYFP expression driven by the CaMKIIα promoter was stronger in the fusiform layer but labelled cells showed a diverse morphology indicating that they belong to different classes of DCN neurons. Light stimulation after driving Channelrhodopsin2 (ChR2) by the CaMKIIα promoter generated spikes in some units but firing rate decreased when light stimulation coincide with sound presentation. Expression and activation of eArch3.0 (CaMKIIα driven) in the DCN produced spike inhibition in some units but, most importantly, sound-driven spikes were delayed by concomitant light stimulation. We explored the existence of Cre+ cells in the DCN of Chrna2-Cre mice by hydrogel embedding technique (CLARITY). There were almost no Cre+ cell bodies in the DCN; however, we observed profuse projections arising from the ventral cochlear nucleus (VCN). Anterograde labeling Cre dependent AAV injected in the VCN revealed two main projections: one arising in the ipsilateral superior olive and the contralateral medial nucleus of the trapezoid body (bushy cells) and a second bundle terminating in the DCN, suggesting the latter to be excitatory Chrna2+ T-stellate cells). Stimulating ChR2 expressing terminals (light applied on the DCN) of VCN Chrna2+ cells increased firing of sound responding and nonresponding DCN units. This work shows that molecular tools intensively used in cortical studies may be useful for manipulating the DCN especially in tinnitus studies.

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