scholarly journals Distinct Functional and Anatomical Architecture of the Endocannabinoid System in the Auditory Brainstem

2009 ◽  
Vol 101 (5) ◽  
pp. 2434-2446 ◽  
Author(s):  
Yanjun Zhao ◽  
Maria E. Rubio ◽  
Thanos Tzounopoulos
Keyword(s):  
Molecular Layer ◽  
Endocannabinoid System ◽  
Auditory Brainstem ◽  
Dorsal Cochlear Nucleus ◽  
Parallel Fibers ◽  
Histological Techniques ◽  
Brainstem Nucleus ◽  
Electron Microscopical ◽  
Arachidonoyl Glycerol ◽  
Cartwheel Cells

Endocannabinoids (ECs) act as retrograde messengers that enable postsynaptic cells to regulate the strength of their synaptic inputs. Here, by using physiological and histological techniques, we showed that, unlike in other parts of the brain, excitatory inputs are more sensitive than inhibitory inputs to EC signaling in the dorsal cochlear nucleus (DCN), an auditory brainstem nucleus. The principal cells of the DCN, fusiform cells, integrate acoustic signals through nonplastic synapses located in the deep layer with multimodal sensory signals carried by plastic parallel fibers in the molecular layer. Parallel fibers contact fusiform cells and inhibitory interneurons, the cartwheel cells, which in turn inhibit fusiform cells. Postsynaptic depolarization or pairing of postsynaptic potentials (PSPs) with action potentials (APs) induced EC-mediated modulation of excitatory inputs but did not affect inhibitory inputs. Quantitative electron microscopical studies showed that glutamatergic terminals express more cannabinoid 1 receptors (CB1Rs) than glycinergic terminals. Fusiform and cartwheel cells express diacylglycerol lipase α and β (DGLα/β), the two enzymes involved in the generation of the EC, 2-arachidonoyl-glycerol (2-AG). DGLα and DGLβ are found in the spines of cartwheel but not fusiform cells indicating that the synthesis of ECs is more distant from parallel fiber synapses in fusiform than cartwheel cells. The differential localization and density of DGLα/β and CB1Rs leads to cell- and input-specific EC signaling that favors activity-dependent EC-mediated suppression at synapses between parallel fibers and cartwheel cell spines, thus leading to reduced feedforward inhibition in fusiform cells. We propose that EC signaling is a major modulator of the balance of excitation and inhibition in auditory circuits.

scholarly journals Molecular Layer Inhibitory Interneurons Provide Feedforward and Lateral Inhibition in the Dorsal Cochlear Nucleus

2010 ◽  
Vol 104 (5) ◽  
pp. 2462-2473 ◽  
Author(s):  
Michael T. Roberts ◽  
Laurence O. Trussell
Keyword(s):  
Brain Stem ◽  
Lateral Inhibition ◽  
Cochlear Nucleus ◽  
Molecular Layer ◽  
Dorsal Cochlear Nucleus ◽  
Inhibitory Input ◽  
Auditory Information ◽  
Parallel Fibers ◽  
Sensory Inputs ◽  
Cartwheel Cells

In the outer layers of the dorsal cochlear nucleus, a cerebellum-like structure in the auditory brain stem, multimodal sensory inputs drive parallel fibers to excite both principal (fusiform) cells and inhibitory cartwheel cells. Cartwheel cells, in turn, inhibit fusiform cells and other cartwheel cells. At the microcircuit level, it is unknown how these circuit components interact to modulate the activity of fusiform cells and thereby shape the processing of auditory information. Using a variety of approaches in mouse brain stem slices, we investigated the synaptic connectivity and synaptic strength among parallel fibers, cartwheel cells, and fusiform cells. In paired recordings of spontaneous and evoked activity, we found little overlap in parallel fiber input to neighboring neurons, and activation of multiple parallel fibers was required to evoke or alter action potential firing in cartwheel and fusiform cells. Thus neighboring neurons likely respond best to distinct subsets of sensory inputs. In contrast, there was significant overlap in inhibitory input to neighboring neurons. In recordings from synaptically coupled pairs, cartwheel cells had a high probability of synapsing onto nearby fusiform cells or other nearby cartwheel cells. Moreover, single cartwheel cells strongly inhibited spontaneous firing in single fusiform cells. These synaptic relationships suggest that the set of parallel fibers activated by a particular sensory stimulus determines whether cartwheel cells provide feedforward or lateral inhibition to their postsynaptic targets.

Cartwheel and superficial stellate cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices

1993 ◽  
Vol 69 (5) ◽  
pp. 1384-1397 ◽  
Author(s):  
S. Zhang ◽  
D. Oertel
Keyword(s):  
Cochlear Nucleus ◽  
Nerve Root ◽  
Action Potentials ◽  
Stellate Cell ◽  
Molecular Layer ◽  
Dorsal Cochlear Nucleus ◽  
Fusiform Cell ◽  
Parasagittal Plane ◽  
Axonal Arbors ◽  
Cartwheel Cells

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.

scholarly journals Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious?

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1845
Author(s):  
Stephen Schultz ◽  
Georgianna G. Gould ◽  
Nicola Antonucci ◽  
Anna Lisa Brigida ◽  
Dario Siniscalco
Keyword(s):  
Autism Spectrum Disorder ◽  
Cannabinoid Receptors ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Blood Levels ◽  
Increased Risk ◽  
Patterns Of Behavior ◽  
Arachidonoyl Glycerol

Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.This mini-review article summarizes the current knowledge on this topic.

Auditory processing of complex sounds: an overview

1992 ◽  
Vol 336 (1278) ◽  
pp. 295-306 ◽  
Keyword(s):  
Auditory System ◽  
Auditory Processing ◽  
Dynamic Range ◽  
Auditory Brainstem ◽  
Frequency Selectivity ◽  
Dorsal Cochlear Nucleus ◽  
Cochlear Nerve ◽  
Complex Sounds ◽  
Wide Range ◽  
Time Coding

The past 30 years has seen a remarkable development in our understanding of how the auditory system - particularly the peripheral system - processes complex sounds. Perhaps the most significant has been our understanding of the mechanisms underlying auditory frequency selectivity and their importance for normal and impaired auditory processing. Physiologically vulnerable cochlear filtering can account for many aspects of our normal and impaired psychophysical frequency selectivity with important consequences for the perception of complex sounds. For normal hearing, remarkable mechanisms in the organ of Corti, involving enhancement of mechanical tuning (in mammals probably by feedback of electro-mechanically generated energy from the hair cells), produce exquisite tuning, reflected in the tuning properties of cochlear nerve fibres. Recent comparisons of physiological (cochlear nerve) and psychophysical frequency selectivity in the same species indicate that the ear’s overall frequency selectivity can be accounted for by this cochlear filtering, at least in band width terms. Because this cochlear filtering is physiologically vulnerable, it deteriorates in deleterious conditions of the cochlea - hypoxia, disease, drugs, noise overexposure, mechanical disturbance - and is reflected in impaired psychophysical frequency selectivity. This is a fundamental feature of sensorineural hearing loss of cochlear origin, and is of diagnostic value. This cochlear filtering, particularly as reflected in the temporal patterns of cochlear fibres to complex sounds, is remarkably robust over a wide range of stimulus levels. Furthermore, cochlear filtering properties are a prime determinant of the ‘place’ and ‘time’ coding of frequency at the cochlear nerve level, both of which appear to be involved in pitch perception. The problem of how the place and time coding of complex sounds is effected over the ear’s remarkably wide dynamic range is briefly addressed. In the auditory brainstem, particularly the dorsal cochlear nucleus, are inhibitory mechanisms responsible for enhancing the spectral and temporal contrasts in complex sounds. These mechanisms are now being dissected neuropharmacologically. At the cortical level, mechanisms are evident that are capable of abstracting biologically relevant features of complex sounds. Fundamental studies of how the auditory system encodes and processes complex sounds are vital to promising recent applications in the diagnosis and rehabilitation of the hearing impaired.

scholarly journals Two Distinct Types of Inhibition Mediated by Cartwheel Cells in the Dorsal Cochlear Nucleus

2009 ◽  
Vol 102 (2) ◽  
pp. 1287-1295 ◽  
Author(s):  
Jaime G. Mancilla ◽  
Paul B. Manis
Keyword(s):  
Cochlear Nucleus ◽  
Reversal Potential ◽  
Dorsal Cochlear Nucleus ◽  
Synaptic Function ◽  
Half Width ◽  
Neonatal Rat ◽  
Projection Neurons ◽  
Paired Pulse ◽  
Dependent Inhibition ◽  
Cartwheel Cells

Individual neurons have been shown to exhibit target cell-specific synaptic function in several brain areas. The time course of the postsynaptic conductances (PSCs) strongly influences the dynamics of local neural networks. Cartwheel cells (CWCs) are the most numerous inhibitory interneurons in the dorsal cochlear nucleus (DCN). They are excited by parallel fiber synapses, which carry polysensory information, and in turn inhibit other CWCs and the main projection neurons of the DCN, pyramidal cells (PCs). CWCs have been implicated in “context-dependent” inhibition, producing either depolarizing (other CWCs) or hyperpolarizing (PCs) post synaptic potentials. In the present study, we used paired whole cell recordings to examine target-dependent inhibition from CWCs in neonatal rat DCN slices. We found that CWC inhibitory postsynaptic potentials (IPSPs) onto PCs are large (1.3 mV) and brief (half-width = 11.8 ms), whereas CWC IPSPs onto other CWCs are small (0.2 mV) and slow (half-width = 36.8 ms). Evoked IPSPs between CWCs exhibit paired-pulse facilitation, while CWC IPSPs onto PCs exhibit paired-pulse depression. Perforated-patch recordings showed that spontaneous IPSPs in CWCs are hyperpolarizing at rest with a mean estimated reversal potential of −67 mV. Spontaneous IPSCs were smaller and lasted longer in CWCs than in PCs, suggesting that the kinetics of the receptors are different in the two cell types. These results reveal that CWCs play a dual role in the DCN. The CWC-CWC network interactions are slow and sensitive to the average rate of CWC firing, whereas the CWC-PC network is fast and sensitive to transient changes in CWC firing.

Distal Versus Proximal Inhibitory Shaping of Feedback Excitation in the Electrosensory Lateral Line Lobe: Implications for Sensory Filtering

1998 ◽  
Vol 80 (6) ◽  
pp. 3214-3232 ◽  
Author(s):  
Neil J. Berman ◽  
Leonard Maler
Keyword(s):  
Lateral Line ◽  
Pyramidal Cell ◽  
Stellate Cell ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Stellate Cells ◽  
Decay Phase ◽  
Tetanic Stimulation ◽  
Parallel Fibers ◽  
Cell Inhibition

Berman, Neil J. and Leonard Maler. Distal versus proximal inhibitory shaping of feedback excitation in the electrosensory lateral line lobe: implications for sensory filtering. J. Neurophysiol. 80: 3214–3232, 1998. The inhibition controlling the indirect descending feedback (parallel fibers originating from cerebellar granule cells in the eminentia posterior pars granularis) to electrosensory lateral line lobe (ELL) pyramidal cells was studied using intracellular recording techniques in vitro. Parallel fibers (PF) contact stellate cells and dendrites of ventral molecular layer (VML) GABAergic interneurons. Stellate cells provide local input to pyramidal cell distal dendrites, whereas VML cells contact their somata and proximal dendrites. Single-pulse stimulation of PF evoked graded excitatory postsynaptic potentials (EPSPs) that were blocked by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-d-aspartate (NMDA) antagonists. The EPSPs peaked at 6.4 ± 1.8 ms (mean ± SE; n = 11) but took >50 ms to decay completely. Tetanic stimulation (100 ms, 100 Hz) produced a depolarizing wave with individual EPSPs superimposed. The absolute amplitude of the individual EPSPs decreased during the train. Spike rates, established by injected current, mostly were increased, but in some cells were decreased, by tetanic stimulation. Global application of a γ-aminobutyric acid-A (GABAA) antagonist to the recorded cell's soma and apical dendritic region increased the EPSP peak and decay phase amplitudes. Tetanic stimulation always increased current-evoked spike rates after GABAA blockade during, and for several hundred milliseconds after, the stimulus. Application of a GABAB antagonist did not have any significant effects on the PF-evoked response. This, and the lack of any long hyperpolarizing inhibitory postsynaptic potentials, suggests that VML and stellate cell inhibition does not involve GABAB receptors. Focal GABAA antagonist applications to the dorsal molecular layer (DML) and pyramidal cell layer (PCL) had contrasting effects on PF-evoked EPSPs. DML GABAA blockade significantly increased the EPSP peak amplitude but not the decay phase of the EPSP, whereas PCL GABAA-blockade significantly increased the decay phase, but not the EPSP peak, amplitude. The order of antagonist application did not affect the outcome. On the basis of the known circuitry of the ELL, we conclude that the distal inhibition originated from GABAergic molecular layer stellate cells and the proximal inhibition originated from GABAergic cells of the ventral molecular layer (VML cells). Computer modeling of distal and proximal inhibition suggests that intrinsic differences in IPSP dynamics between the distal and proximal sites may be amplified by voltage-dependent NMDA receptor and persistent sodium currents. We propose that the different time courses of stellate cell and VML cell inhibition allows them to act as low- and high-pass filters respectively on indirect descending feedback to ELL pyramidal cells.

Anisotropic and heterogeneous diffusion in the turtle cerebellum: implications for volume transmission

1993 ◽  
Vol 70 (5) ◽  
pp. 2035-2044 ◽  
Author(s):  
M. E. Rice ◽  
Y. C. Okada ◽  
C. Nicholson
Keyword(s):  
Time Course ◽  
Granular Layer ◽  
Volume Fraction ◽  
Molecular Layer ◽  
Extracellular Volume ◽  
Striking Difference ◽  
Volume Transmission ◽  
Anisotropic Porous Media ◽  
Parallel Fibers ◽  
Ion Shifts

1. Measurements of extracellular diffusion properties were made in three orthogonal axes of the molecular and granular layers of the isolated turtle cerebellum with the use of iontophoresis of tetramethylammonium (TMA+) combined with ion-selective microelectrodes. 2. Diffusion in the extracellular space of the molecular layer was anisotropic, that is, there was a different value for the tortuosity factor, lambda i, associated with each axis of that layer. The x- and y-axes lay in the plane parallel to the pial surface of this lissencephalic cerebellum with the x-axis in the direction of the parallel fibers. The z-axis was perpendicular this plane. The tortuosity values were lambda x = 1.44 +/- 0.01, lambda y = 1.95 +/- 0.02, and lambda z = 1.58 +/- 0.01 (mean +/- SE). By contrast, the granular layer was isotropic with a single tortuosity value, lambda Gr = 1.77 +/- 0.01. 3. These data confirm the applicability of appropriately extended Fickian equations to describe diffusion in anisotropic porous media, including brain tissue. 4. Heterogeneity between the molecular and granular layer was revealed by a striking difference in extracellular volume fraction, alpha, for each layer. In the molecular layer alpha = 0.31 +/- 0.01, whereas in the granular layer alpha = 0.22 +/- 0.01. 5. Volume fraction and tortuosity affected the time course and amplitude of extracellular TMA+ concentration after iontophoresis. This was modeled by the use of the average parameters determined experimentally, and the nonspherical pattern of diffusion in the molecular layer was compared with the spherical distribution in the granular layer and agarose gel by computing isoconcentration ellipsoids. 6. One functional consequence of these results was demonstrated by measuring local changes in [K+]o and [Ca2+]o after microiontophoresis of a cerebellar transmitter, glutamate. The ratios of ion shifts in the x- and y-axes in the granular layer were close to unity, with a ratio of 1.04 +/- 0.08 for the rise in [K+]o and 1.03 +/- 0.17 for the decrease in [Ca2+]o. In contrast, ion shifts in the molecular layer had an x:y ratio of 1.44 +/- 0.14 for the rise in [K+]o and 2.10 +/- 0.42 for the decrease in [Ca2+]o. 7. These data demonstrate that the structure of cellular aggregates can channel the migration of substances in the extracellular microenvironment, and this could be a mechanism for volume transmission of chemical signals. For example, the preferred diffusion direction of glutamate along the parallel fibers would help constrain an incoming excitatory stimulus to stay "on-beam."

Vertical Cell Responses to Sound in Cat Dorsal Cochlear Nucleus

1999 ◽  
Vol 82 (2) ◽  
pp. 1019-1032 ◽  
Author(s):  
William S. Rhode
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Molecular Layer ◽  
Broadband Noise ◽  
Dorsal Cochlear Nucleus ◽  
Type Ii ◽  
Fusiform Cell ◽  
Sound Sources ◽  
Tuning Curves ◽  
Axonal Arbors

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.

Physiological studies on neurons in the dorsal cochlear nucleus of cat

1986 ◽  
Vol 56 (2) ◽  
pp. 287-307 ◽  
Author(s):  
W. S. Rhode ◽  
P. H. Smith
Keyword(s):  
Spontaneous Activity ◽  
Cochlear Nucleus ◽  
Response Pattern ◽  
Phase Locking ◽  
Molecular Layer ◽  
Dorsal Cochlear Nucleus ◽  
Fusiform Cell ◽  
Graded Response ◽  
Temporal Encoding ◽  
Onset Response

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.

scholarly journals Revealing the molecular layer of the primate dorsal cochlear nucleus

Neuroscience ◽  
2008 ◽  
Vol 154 (1) ◽  
pp. 99-113 ◽  
Author(s):  
M.E. Rubio ◽  
K.A. Gudsnuk ◽  
Y. Smith ◽  
D.K. Ryugo
Keyword(s):  
Cochlear Nucleus ◽  
Molecular Layer ◽  
Dorsal Cochlear Nucleus
Sign in / Sign up

Export Citation Format

Share Document