scholarly journals Intrinsic and synaptic properties of vertical cells of the mouse dorsal cochlear nucleus

2012 ◽  
Vol 108 (4) ◽  
pp. 1186-1198 ◽  
Author(s):  
Sidney P. Kuo ◽  
Hsin-Wei Lu ◽  
Laurence O. Trussell

Multiple classes of inhibitory interneurons shape the activity of principal neurons of the dorsal cochlear nucleus (DCN), a primary target of auditory nerve fibers in the mammalian brain stem. Feedforward inhibition mediated by glycinergic vertical cells (also termed tuberculoventral or corn cells) is thought to contribute importantly to the sound-evoked response properties of principal neurons, but the cellular and synaptic properties that determine how vertical cells function are unclear. We used transgenic mice in which glycinergic neurons express green fluorescent protein (GFP) to target vertical cells for whole cell patch-clamp recordings in acute slices of DCN. We found that vertical cells express diverse intrinsic spiking properties and could fire action potentials at high, sustained spiking rates. Using paired recordings, we directly examined synapses made by vertical cells onto fusiform cells, a primary DCN principal cell type. Vertical cell synapses produced unexpectedly small-amplitude unitary currents in fusiform cells, and additional experiments indicated that multiple vertical cells must be simultaneously active to inhibit fusiform cell spike output. Paired recordings also revealed that a major source of inhibition to vertical cells comes from other vertical cells.

1993 ◽  
Vol 69 (5) ◽  
pp. 1384-1397 ◽  
Author(s):  
S. Zhang ◽  
D. Oertel

1. Intracellular recordings were made from identified cartwheel and stellate cells in the molecular and fusiform cell layers of the murine dorsal cochlear nucleus (DCN). The aim of the study was to identify and characterize their synaptic inputs and to learn how synaptic inputs and intrinsic electrical properties interact to generate firing patterns. 2. Eight cells labeled by the intracellular injection of biocytin were cartwheel cells. Their axon terminals extended from the deep part of the molecular layer through the fusiform cell layer. Their dendrites extended through the molecular layer and had spines. Both the dendritic and axonal arbors were small, having diameters of approximately 150 microns in the parasagittal plane. 3. When depolarized, cartwheel cells often fired bursts of rapid action potentials superimposed on a slow depolarization. The peaks of action potentials were usually overshooting. Individually occurring action potentials were followed by two afterhyperpolarizations, as in other cells of the DCN. During bursts, action potentials did not have two distinct repolarizing phases. 4. Excitatory postsynaptic potentials (EPSPs) were recorded from cartwheel cells spontaneously and after shocks to the nerve root or to the ventral cochlear nucleus (VCN). The EPSPs rose slowly. When they were suprathreshold they evoked action potentials singly or in bursts. EPSPs evoked by shocks to the nerve root or to the VCN had long latencies, the rise of EPSPs beginning between 5 and 10 ms after the shock. No inhibitory synaptic potentials, either spontaneous or driven with electrical stimulation, were detected in cells whose resting potentials were between -50 and -70 mV. 5. The locations from which excitatory input can be driven electrically are consistent with cartwheel cells receiving excitatory synaptic input from granule cells. 6. One labeled cell was a superficial stellate cell. It had smooth, straight dendrites that radiated parallel to the layers of the DCN; its axonal arbor was also planar and was restricted to the molecular layer. Both the dendritic and axonal arbors of this stellate cell were large, > 500 microns diam in the parasagittal plane. 7. The superficial stellate cell fired trains of action potentials at regular intervals that, like other cells of the DCN, were overshooting and were followed by double undershoots. 8. Shocks to the nerve root and to the surface of the VCN evoked EPSPs after 3.5 and 2 ms, respectively, in the superficial stellate cell. Chemical stimulation of the VCN also evoked excitation. No inhibitory synaptic input, spontaneous or driven, was detected.


2001 ◽  
Vol 280 (1) ◽  
pp. C175-C182 ◽  
Author(s):  
Michihiro Tateyama ◽  
Shuqin Zong ◽  
Tsutomu Tanabe ◽  
Rikuo Ochi

Using the whole-cell patch-clamp technique, we have studied the properties of α1ECa2+ channel transfected in cardiac myocytes. We have also investigated the effect of foreign gene expression on the intrinsic L-type current ( I Ca,L). Expression of green fluorescent protein significantly decreased the I Ca,L. By contrast, expression of α1E with β2b and α2/δ significantly increased the total Ca2+ current, and in these cells a Ca2+ antagonist, PN-200-110 (PN), only partially blocked the current. The remaining PN-resistant current was abolished by the application of a low concentration of Ni2+and was little affected by changing the charge carrier from Ca2+ to Ba2+ or by β-adrenergic stimulation. On the basis of its voltage range for activation, this channel was classified as a high-voltage activated channel. Thus the expression of α1E did not generate T-like current in cardiac myocytes. On the other hand, expression of α1E decreased I Ca,L and slowed the I Ca,L inactivation. This inactivation slowing was attenuated by the β2b coexpression, suggesting that the α1E may slow the inactivation of I Ca,L by scrambling with α1C for intrinsic auxiliary β.


1999 ◽  
Vol 82 (2) ◽  
pp. 1019-1032 ◽  
Author(s):  
William S. Rhode

The dorsal cochlear nucleus receives input from the auditory nerve and relays acoustic information to the inferior colliculus. Its principal cells receive two systems of inputs. One system through the molecular layer carries multimodal information that is processed through a neuronal circuit that resembles the cerebellum. A second system through the deep layer carries primary auditory nerve input, some of which is relayed through interneurons. The present study reveals the morphology of individual interneurons and their local axonal arbors and how these inhibitory interneurons respond to sound. Vertical cells lie beneath the fusiform cell layer. Their dendritic and axonal arbors are limited to an isofrequency lamina. They give rise to pericellular nests around the base of fusiform cells and their proximal basal dendrites. These cells exhibit an onset-graded response to short tones and have response features defined as type II. They have tuning curves that are closed contours (0 shaped), thresholds ∼27 dB SPL, spontaneous firing rates of ∼0 spikes/s, and they respond weakly or not at all to broadband noise, as described for type II units. Their responses are nonmonotonic functions of intensity with peak responses between 30 and 60 dB SPL. They also show a preference for the high-to-low direction of a frequency sweep. It has been suggested that these circuits may be involved in the processing of spectral cues for the localization of sound sources.


1986 ◽  
Vol 56 (2) ◽  
pp. 287-307 ◽  
Author(s):  
W. S. Rhode ◽  
P. H. Smith

Results reported here support the conclusion that an individual neuron in the dorsal cochlear nucleus (DCN) can exhibit pauser, buildup, and chopper patterns in response to tone pips. Fusiform cells have been previously identified as the principal cell exhibiting these patterns. Fusiform cells can also exhibit an onset response followed by suppression of spontaneous activity at their characteristic frequency (CF). Off CF only suppression is seen. These neurons are characterized by a restricted excitatory region near threshold. All these cells can exhibit nonmonotonic rate curves, narrow excitatory regions, and inhibitory sidebands. Nonmonotonicity occurred in 34% of pausers, 52% of buildup, 89% of onsets with a graded response, and 50% overall in the DCN cells. Chopper units occur as often as the other types combined in the DCN. Only 14% show nonmonotonic rate curves. Those with high-spontaneous activity also show inhibitory sidebands. Cells with a predominant buildup pattern occur most frequently in the fusiform cell layer, whereas pausers occur throughout the DCN below the molecular layer. Intracellular potentials often reflect the average response pattern. Sharply delimited response areas indicate that these cells may be useful for performing a spectral analysis. These cells show almost no phase locking suggesting that temporal encoding is an unlikely function. It is suggested that the effects of anesthetic on the function of the DCN is not as marked as previously indicated.


2008 ◽  
Vol 99 (4) ◽  
pp. 2026-2032 ◽  
Author(s):  
Long-Jun Wu ◽  
Min Zhuo

Microglia are well known for their roles in brain injuries and infections. However, there is no function attributes to resting microglia thus far. Here we performed a combination of simultaneous electrophysiology and time-lapse confocal imaging in green fluorescent protein–labeled microglia in acute hippocampal slices. In contrast to CA1 neurons, microglia showed no spontaneous or evoked synaptic currents. Neither glutamate- nor GABA-induced current/chemotaxis of microglia was detected. Strong tetanic stimulation of Schaffer-collateral pathways that induce CA1 long-term potentiation did not affect microglial motilities. Our results suggest that microglia are highly reserved for neuronal protective function but not synaptic plasticity in the brain.


2021 ◽  
Author(s):  
Hu Zhou ◽  
Jingxin Zhang ◽  
Huaxiang Shi ◽  
Pengfei Li ◽  
Xin Sui ◽  
...  

Abstract Dysfunction of striatal dopaminergic circuits has been implicated in motor impairment as well as in Parkinson’s disease (PD)-related circadian perturbations that may represent an early prodromal marker of PD. Cyclin-dependent kinase 5 (CDK5) acts negatively on dopamine (DA) signaling in the striatum, suggesting a critical role in circadian and sleep disorders. Here, we used CRISPR/Cas9 gene editing to produce dorsal striatum (DS)-specific knockdown (KD) of the Cdk5 gene in mice (referred to as DS-CDK5-KD mice) to investigate its role in vivo. DS-CDK5-KD mice exhibited deficits in locomotor activity and disturbances in daily rest/activity cycles. Additionally, Golgi staining of neurons in the DS revealed that Cdk5 deletion caused a reduction in dendrite length and functional synapses, which was confirmed by significant downregulation of MAP2, PSD95 and synapsin I. Correlated with this, DS-CDK5-KD mice displayed reduced phosphorylation of Tau at Thr181. Furthermore, whole-cell patch-clamp recordings of green fluorescent protein (GFP)-tagged neurons in the striatum of DS-CDK5-KD mice revealed a decrease in the frequency of spontaneous inhibitory post-synaptic currents and an alteration of the excitatory/inhibitory synaptic balance. Notably, anterograde labeling showed that CDK5 knockdown in the DS disrupted long-range projections to the secondary motor cortex, dorsal and ventral thalamic nuclei, and the basolateral amygdala, which are involved in the regulation of motor and circadian rhythms in the brain. These findings support a critical role of CDK5 in the DS in maintaining the striatal neural circuitry underlying motor and circadian rhythms related to PD.


Neuroscience ◽  
2019 ◽  
Vol 407 ◽  
pp. 170-181 ◽  
Author(s):  
David T. Martel ◽  
Thibaut R. Pardo-Garcia ◽  
Susan E. Shore

1994 ◽  
Vol 71 (2) ◽  
pp. 467-478 ◽  
Author(s):  
H. J. Waller ◽  
D. A. Godfrey

1. The cochlear nucleus of rat brain stem slices was explored with extracellular microelectrodes to determine the distribution and characteristics of spontaneously active neurons. 2. In mapping experiments few spontaneously active neurons were found in anteroventral or posteroventral divisions of the cochlear nucleus. In contrast, spontaneously active neurons (N = 648) were widely distributed in the dorsal cochlear nucleus (DCN), especially its more superficial part. The density (neurons per penetration) was greatest 100-400 microns from the lateral surface of DCN, corresponding approximately to the fusiform soma layer and closely adjacent portions of the molecular and deeper regions. In penetrations with active neurons as many as 13 were found, with a mean of 4.3 neurons per penetration. Activity was found along the entire dorsomedial-ventrolateral extent of the nucleus, across the tonotopic representation. 3. Most neurons were readily categorized according to the spike interval pattern as regular (40%), bursting (30%), or irregular (30%). Regular and bursting patterns were highly stable, but few bursting neurons were found in relatively inactive slices. Although there was extensive overlap in location, bursting neurons were significantly closer to the lateral edge of the slice. Also, they were more likely to have initially negative action potentials than regular or irregular neurons. 4. A high density of spontaneous firing, including regular, bursting, and irregular patterns, was observed in slices containing only DCN and adjacent fiber tracts, with other nuclear structures trimmed away. 5. When the K+ concentration of the perfusion medium was decreased from 6.25 to 3.25 mM firing rates of regular neurons decreased moderately without changes in pattern. In contrast, firing rates of most bursting and irregular neurons showed large increases, and bursts were prolonged. 6. When the K+ concentration was increased from 6.25 to 9.25 or 12.25 mM regular neurons showed moderate increases in rate without changes in pattern. Effects on firing rates differed among bursting and irregular neurons, but bursts usually increased in frequency and decreased in duration, and irregular neurons showed some burst firing. 7. When Ca2+ was decreased to 0.2 mM and Mg2+ increased to 3.8 or 7.8 mM regular neurons did not change in pattern of firing although firing rates increased or decreased moderately. Bursting neurons showed large increases in the durations of the bursts. Firing rates of bursting neurons usually increased during 0.2 mM Ca2+ -3.8 mM Mg2+ but typically decreased, after an initial rise, during 0.2 mM Ca2+ -7.8 mM Mg2+.(ABSTRACT TRUNCATED AT 400 WORDS)


1994 ◽  
Vol 71 (3) ◽  
pp. 914-930 ◽  
Author(s):  
S. Zhang ◽  
D. Oertel

1. Intracellular recordings were made from 21 anatomically identified fusiform cells in the dorsal cochlear nucleus (DCN) of mice in slices. The aim of the experiments was to dissect the synaptic responses to shocks of the auditory nerve to correlate functional characteristics with the different classes of synaptic inputs. 2. When depolarized from rest (-57 +/- 5 mV) with current pulses, fusiform cells fired regular, overshooting action potentials that were followed by two undershoots. The frequency of firing increased with the strength of injected current by between 100 and 300 spikes/s/nA. The current-voltage relationship rectified between 10 and 15 mV below the resting potential. The slopes of current-voltage relationships of fusiform cells in the range between the resting potential and 10 mV hyperpolarization indicated an average input resistance of 86 +/- 37 M omega. 3. In each of the labeled fusiform cells frequent, spontaneous inhibitory postsynaptic potentials (IPSPs) were recorded singly or in bursts. Some, but not all, IPSPs were preceded by a slowly rising excitatory postsynaptic potential (EPSP). The temporal association of spontaneous EPSPs and IPSPs suggests that they are driven by a common source, possibly granule cells. 4. Shocks to the auditory nerve evoked synaptic responses consisting of early (1 to approximately 10 ms) and late (approximately 10 to 100 ms) components. 6,7-Dinitroquinoxaline-2,3-dione (DNQX) at 20 to 40 microM eliminated all detectable excitation and all late IPSPs. Late bursts of IPSPs, therefore, are mediated through a polysynaptic pathway that includes a DNQX-sensitive stage. Strong shocks to the nerve root elicited single monosynaptic IPSPs, indicating that inhibitory interneurons have processes close to the auditory nerve. Strychnine at 0.5 microM eliminated all detectable inhibition. 6. Cuts through the posteroventral cochlear nucleus (PVCN), which severed the descending branches of auditory nerve fibers, eliminated early EPSPs and IPSPs leaving late, slowly rising EPSPs and bursts of IPSPs in responses to shocks of the auditory nerve. Late, slowly rising EPSPs and bursts of IPSPs, as well as monosynaptic IPSPs, could also be evoked by stimulating the anteroventral cochlear nucleus (AVCN). 7. Focal applications of glutamate evoked excitation and inhibition from many parts of a slice, with patterns varying among cells, indicating that fusiform cells receive inputs through several groups of interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)


2007 ◽  
Vol 98 (4) ◽  
pp. 2133-2143 ◽  
Author(s):  
Lina A. J. Reiss ◽  
Sharba Bandyopadhyay ◽  
Eric D. Young

Neurons in the dorsal cochlear nucleus (DCN) exhibit strong nonlinearities in spectral processing. Low-order models that transform the stimulus spectrum into discharge rate using a combination of first- and second-order weighting of the spectrum (quadratic models) usually fail to predict responses to novel stimuli for principal neurons in the DCN, even though they work well in ventral cochlear nucleus. Here we investigate the effects of spectral contrast on the performance of such models. Typically, the models fail for stimuli with natural-sound–like spectral contrasts (∼12 dB), but have good prediction performance at small (3-dB) contrasts. The weights also typically increase substantially in amplitude at smaller spectral contrast. These changes in weight size with contrast are partly inherited from similar effects seen in auditory nerve fibers, but there must be additional effects from inhibitory circuits in the DCN. These results provide insight into the reasons for the poor performance of spectrotemporal receptive field (STRF) models in predicting responses of auditory neurons. Because the general shapes of the weights do not change between low and high contrast, they also suggest that STRFs may capture meaningful properties of neural receptive fields, even though they do not do well at predicting responses.


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