Lamina-Specific Deficits in Parvalbumin-Immunoreactive Varicosities in the Prefrontal Cortex of Subjects With Schizophrenia: Evidence for Fewer Projections From the Thalamus

Lewis, David A.; Cruz, Dianne A.; Melchitzky, Darlene S.; Pierri, Joseph N.

doi:10.1176/appi.ajp.158.9.1411

Cited by 177 publications

(112 citation statements)

References 46 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…On the basis of their connectivity with pyramidal neurons, as well as with each other, PV-expressing interneurons are effectively positioned to participate in network oscillatory activity within the HPC. In patients with schizophrenia, as well as in animal models of the disease, a significant reduction in PV has been reported in cortical as well as HPC areas (Hashimoto et al, 2003;Lewis et al, 2001;Lodge et al, 2009;Tseng et al, 2008). The loss of PV corresponds with a pathological alteration in oscillatory activity with broad consequences on network dynamics between brain regions.…”

Section: Discussionmentioning

confidence: 99%

A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia

Gill

Lodge

Cook

et al. 2011

Neuropsychopharmacol

153

181

View full text Add to dashboard Cite

We have shown previously that aberrant hippocampal (HPC) output underlies the dopamine (DA) dysfunction observed in the methylazoxymethanol acetate (MAM) developmental model of schizophrenia in the rodent. This alteration of HPC activity was proposed to result from a reduction in parvalbumin (PV)-expressing GABAergic interneurons and consequent destabilization of the output of pyramidal neurons, as well as disrupted activation across a broad neural network. In vivo extracellular recordings were performed in the ventral tegmental area (VTA) and ventral HPC of saline-(SAL) and MAM-treated animals. A novel benzodiazepine-positive allosteric modulator (PAM), selective for the a5 subunit of the GABA A receptor, SH-053-2 0 F-R-CH3, was tested for its effects on the output of the HPC, leading to dopamine system hyperactivity in MAM-treated animals. In addition, the effect of SH-053-2 0 F-R-CH3 on the hyperactive locomotor response to amphetamine in MAM animals was examined. We demonstrate that treatment with the a5GABA A R PAM reduced the number of spontaneously active DA neurons in the VTA of MAM animals to levels observed in SAL rats, both when administered systemically and when directly infused into the ventral HPC. Moreover, HPC neurons in both SAL and MAM animals showed diminished cortical-evoked responses following a5GABA A R PAM treatment. In addition, the increased locomotor response to amphetamine observed in MAM rats was reduced following a5GABA A R treatment. This study supports a novel treatment of schizophrenia that targets abnormal HPC output, which in turn normalizes dopaminergic neuronal activity.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia

Gill

Lodge

Cook

et al. 2011

Neuropsychopharmacol

153

181

View full text Add to dashboard Cite

show abstract

“…As discussed in this same review (Lewis et al 2005), some experimental work exists indicating possible alteration to synaptic kinetics of cortical basket cells. Upregulation in postsynaptic GABA receptors in schizophrenia has been localized in cortical pyramidal cell bodies, where basket cells are known to form synaptic contact (Benes et al 1996) and a significant reduction in parvalbumin immunoreactive varicosities, which may correspond to the axon terminals of basket cells, has been found in the middle cortical layers in prefrontal cortex (Lewis et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Modeling Gaba Alterations in Schizophrenia: A Link Between Impaired Inhibition and Altered Gamma and Beta Range Auditory Entrainment

Vierling-Claassen¹,

Siekmeier²,

Stufflebeam³

2008

Schizophrenia Research

View full text Add to dashboard Cite

Vierling-Claassen D, Siekmeier P, Stufflebeam S, Kopell N. Modeling GABA alterations in schizophrenia: a link between impaired inhibition and altered gamma and beta range auditory entrainment. J Neurophysiol 99: 2656 -2671, 2008. First published February 20, 2008 doi:10.1152/jn.00870.2007. The disorganized symptoms of schizophrenia, including severely disordered thought patterns, may be indicative of a problem with the construction and maintenance of cell assemblies during sensory processing and attention. The gamma and beta frequency bands (15-70 Hz) are believed relevant to such processing. This paper addresses the results of an experimental examination of the cortical response of 12 schizophrenia patients and 12 control subjects when presented with auditory click-train stimuli in the gamma/beta frequency band during measurement using magnetoencephalography (MEG), as well as earlier work by Kwon et al. These data indicate that control subjects show an increased 40-Hz response to both 20-and 40-Hz stimulation as compared with patients, whereas schizophrenic subjects show a preference for 20-Hz response to the same driving frequencies. In this work, two computational models of the auditory cortex are constructed based on postmortem studies that indicate cortical interneurons in schizophrenic subjects have decreased GAT-1 (a GABA transporter) and GAD 67 (1 of 2 enzymes responsible for GABA synthesis). The models transition from control to schizophrenic frequency response when an extended inhibitory decay time is introduced; this change captures a possible effect of these GABA alterations. Modeling gamma/beta range auditory entrainment in schizophrenia provides insight into how biophysical mechanisms can impact cognitive function. In addition, the study of dynamics that underlie auditory entrainment in schizophrenia may contribute to the understanding of how gamma and beta rhythms impact cognition in general.

show abstract

“…The widespread prefrontal projections to TRN from these cortices may help focus attention on relevant and motivationally salient stimuli. In schizophrenia, both lateral prefrontal cortex and MD are disrupted / 19,61,63,97,135,137,147,169,177 /, potentially impairing the ability to effectively select relevant stimuli and suppress distractors. Features of TRN neurons.…”

Section: Model Of Prefrontal Influence In Attentional Modulation Thromentioning

confidence: 99%

Circuits for Multisensory Integration and Attentional Modulation Through the Prefrontal Cortex and the Thalamic Reticular Nucleus in Primates

Zikopoulos

Barbas²

2007

Reviews in the Neurosciences

134

111

View full text Add to dashboard Cite

Converging evidence from anatomic and physiologic studies suggests that the interaction of highorder association cortices with the thalamus is necessary to focus attention on a task in a complex environment with multiple distractions. Interposed between the thalamus and cortex, the inhibitory thalamic reticular nucleus intercepts and regulates communication between the two structures. Recent findings demonstrate that a unique circuitry links the prefrontal cortex with the reticular nucleus and may underlie the process of selective attention to enhance salient stimuli and suppress irrelevant stimuli in behavior. Unlike other cortices, some prefrontal areas issue widespread projections to the reticular nucleus, extending beyond the frontal sector to the sensory sectors of the nucleus and may influence the flow of sensory information from the thalamus to the cortex. Unlike other thalamic nuclei, the mediodorsal nucleus, which is the principal thalamic nucleus for the prefrontal cortex, has similarly widespread connections with the reticular nucleus. Unlike sensory association cortices, some terminations from prefrontal areas to the reticular nucleus are large, suggesting efficient transfer of information. We propose a model showing that the specialized features of prefrontal pathways in the reticular nucleus may allow selection of relevant information and override distractors, in processes that are deranged in schizophrenia.

show abstract

Lamina-Specific Deficits in Parvalbumin-Immunoreactive Varicosities in the Prefrontal Cortex of Subjects With Schizophrenia: Evidence for Fewer Projections From the Thalamus

Cited by 177 publications

References 46 publications

A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia

A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia

Modeling Gaba Alterations in Schizophrenia: A Link Between Impaired Inhibition and Altered Gamma and Beta Range Auditory Entrainment

Circuits for Multisensory Integration and Attentional Modulation Through the Prefrontal Cortex and the Thalamic Reticular Nucleus in Primates

Contact Info

Product

Resources

About