Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia

Sweet, Robert A.; Henteleff, Ruth; Zhang, Wei; Sampson, Allan R.; Lewis, David A.

doi:10.1038/npp.2008.67

Cited by 256 publications

(248 citation statements)

References 116 publications

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“…Such a reduction could certainly account for the differences reported here, especially with respect to reduced cortical source strength. Even more recently this same group has reported a reduction in dendritic spine density in both primary and associative auditory cortices (Sweet, et al, 2008) in the same group of subjects. The SSR has been postulated to represent the activation of a resonant loop between the auditory cortex and the thalamus (e.g., Ribary et al, 1991), and hence a deficit in the pyramidal cell, and/or dendritic spine density, should result in smaller evoked cortical strength estimates as observed here.…”

Section: Discussionmentioning

confidence: 81%

Cortical source estimates of gamma band amplitude and phase are different in schizophrenia

et al. 2008

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Reductions in gamma band phase synchrony and evoked power have been reported in schizophrenic subjects in response to auditory stimuli. These results have been observed in the EEG at one or two electrode sites. We wished to extend these results using magnetic field data to estimate the responses at the neural generators themselves in each hemisphere. Whole head magnetoencephalographic (MEG) recordings were used to estimate the phase and amplitude behavior of sources in primary auditory cortex in both hemispheres of schizophrenic and comparison subjects. Both ipsi-and contralateral cases were evaluated using a driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus. We used source space projection (SSP) to collapse the magnetic field data into estimates of the time course of source strengths in individual trials. Complex wavelet based timefrequency decomposition was used to compute inter-trial phase locking factor (PLF), and mean evoked and induced amplitude for each cortical generator. Schizophrenic subjects showed reduced SSP PLF and evoked source strength for contra-lateral generators responding to the driving stimulus in both hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the transient window were reduced. In contrast, subjects with schizophrenia exhibited higher induced 40 Hz power to both stimulus types, consistent with the reduced PLF findings. The method of SSP combined with wavelet based complex demodulation produces a significant improvement in signal-to-noise ratio, and directly estimates the activity of the cortical generators responsible for gamma band auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment of generation and phase locking of this activity in auditory cortex, suggesting an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell activity.

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Section: Discussionmentioning

confidence: 81%

Cortical source estimates of gamma band amplitude and phase are different in schizophrenia

et al. 2008

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“…47 Reduced somal size of pyramidal neurons and reduced density of dendrites and axon terminals in cortical layer 3 has been demonstrated in the primary auditory cortex and the auditory association cortex in schizophrenia. [48][49][50] Pyramidal neurons in layer 3 in the sensory cortex are involved in feedforwarding sensory signals to higher cortical areas. Sweet et al 49 suggested that the abnormalities observed from postmortem studies may give rise to impaired precision of early auditory processing.…”

Section: Discussionmentioning

confidence: 99%

“…[48][49][50] Pyramidal neurons in layer 3 in the sensory cortex are involved in feedforwarding sensory signals to higher cortical areas. Sweet et al 49 suggested that the abnormalities observed from postmortem studies may give rise to impaired precision of early auditory processing. 51 Deficits in auditory processing, such as reduced tone matching abilities or abnormalities in electroencephalographic activity during early phases of auditory processing are evident in schizophrenia, and may contribute to mechanisms leading to AH.…”

Section: Discussionmentioning

confidence: 99%

Auditory Cortex Characteristics in Schizophrenia: Associations With Auditory Hallucinations

Mørch-Johnsen

Nesvåg

Jørgensen

et al. 2016

Schizophrenia Bulletin

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There were no significant differences between AH+ and AH− patients in cortical thickness in the PT or STG, or in auditory cortex surface area in any of the regions investigated. Group differences in cortical thickness in the left HG was not affected by duration of illness or current antipsychotic medication. Conclusions: AH in schizophrenia patients were related to thinner cortex, but not smaller surface area of the left HG, a region which includes the primary auditory cortex. The results support that structural abnormalities of the auditory cortex underlie AH in schizophrenia.

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“…Images containing monkey sections were acquired on an Olympus IX81 microscope with a spinning disk confocal unit and a Hamamatsu EM-CCD digital camera at 60× magnification. Ten image stacks (512 × 512 pixel; 0.25 μm z step) in layer 4, defined as 50-60% of the pia-to-white matter distance, per each section were selected using a previously published method for systematic random sampling (33). The mean numbers of PVimmunoreactive neurons sampled in the same volume of tissue did not differ between age groups (t 11 = 0.06, P = 0.952).…”

Section: Methodsmentioning

confidence: 99%

Developmental pruning of excitatory synaptic inputs to parvalbumin interneurons in monkey prefrontal cortex

Chung

Wills

Fish

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Working memory requires efficient excitatory drive to parvalbuminpositive (PV) interneurons in the primate dorsolateral prefrontal cortex (DLPFC). Developmental pruning eliminates superfluous excitatory inputs, suggesting that working memory maturation during adolescence requires pruning of excitatory inputs to PV interneurons. Therefore, we tested the hypothesis that excitatory synapses on PV interneurons are pruned during adolescence. The density of excitatory synapses, defined by overlapping vesicular glutamate transporter 1-positive (VGlut1+) and postsynaptic density 95-positive (PSD95+) puncta, on PV interneurons was lower in postpubertal relative to prepubertal monkeys. In contrast, puncta levels of VGlut1 and PSD95 proteins were higher in postpubertal monkeys and positively predicted activity-dependent PV levels, suggesting a greater strength of the remaining synapses after pruning. Because excitatory synapse number on PV interneurons is regulated by erb-b2 receptor tyrosine kinase 4 (ErbB4), whose function is influenced by alternative splicing, we tested the hypothesis that pruning of excitatory synapses on PV interneurons is associated with developmental shifts in ErbB4 expression and/or splicing. Pan-ErbB4 expression did not change, whereas the minor-to-major splice variant ratios increased with age. In cell culture, the major, but not the minor, variant increased excitatory synapse number on PV interneurons and displayed greater kinase activity than the minor variant, suggesting that the effect of ErbB4 signaling in PV interneurons is mediated by alternative splicing. Supporting this interpretation, in monkey DLPFC, higher minor-to-major variant ratios predicted lower PSD95+ puncta density on PV interneurons. Together, our findings suggest that ErbB4 splicing may regulate the pruning of excitatory synapses on PV interneurons during adolescence.synaptic pruning | parvalbumin interneuron | ErbB4 | alternative splicing | schizophrenia I n primates, certain complex cognitive processes, such as working memory, depend in part on the proper activation of specific neural circuits in the dorsolateral prefrontal cortex (DLPFC) (1). In both monkeys and humans, recruitment of DLPFC activity and performance during working memory tasks continue to improve through adolescence (2-4). During this period, excitatory synapses and their principal targets, pyramidal neuron dendritic spines, massively decline in number in the primate DLPFC (5-8). Synaptic pruning is thought to eliminate unwanted or imprecise connections and to strengthen the remaining connections (9, 10), suggesting that this process could contribute to the maturation of working memory function during adolescence.Working memory is thought to emerge from oscillatory activity of DLPFC neurons at gamma frequency (30-80 Hz) (11), which requires the activity of local GABAergic interneurons that express the calcium binding protein parvalbumin (PV) (12, 13). During working memory tasks, excitation from pyramidal neurons recruits PV interneurons, which in turn pro...

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Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia

Cited by 256 publications

References 116 publications

Cortical source estimates of gamma band amplitude and phase are different in schizophrenia

Cortical source estimates of gamma band amplitude and phase are different in schizophrenia

Auditory Cortex Characteristics in Schizophrenia: Associations With Auditory Hallucinations

Developmental pruning of excitatory synaptic inputs to parvalbumin interneurons in monkey prefrontal cortex

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