A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia

Zhang, Zhi Jun; Reynolds, Gavin P.

doi:10.1016/s0920-9964(01)00188-8

Cited by 427 publications

(328 citation statements)

References 30 publications

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“…This decrease appears specific for PV-containing interneurons, which is consistent with the reduction in local inhibitory GABAergic PV neuron staining that has been reported in postmortem studies in human schizophrenia patients (Lewis et al, 2005;Woo et al, 1998;Zhang and Reynolds, 2002). Thus, the reduction in PV interneuron functionality would likely affect the cortical pyramidal neuron output.…”

Section: Modulatory Influence Of Bla On Vhipp-evoked Firing In Mpfc Isupporting

confidence: 85%

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

Esmaeili

Grace

2013

Neuropsychopharmacol

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Evidence indicates that the prefrontal cortex and its regulation by afferent inputs are disrupted in schizophrenia. Using a validated rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM), we examined the convergent projections from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA) in the medial prefrontal cortex (mPFC). In vivo extracellular recordings were done in anesthetized rats to assess how prior stimulation of the BLA or vHipp input to the mPFC affected mPFC responses to subsequent stimulation of these regions. The interstimulus interval (ISI) of the BLA and vHipp pulse stimulation was varied randomly between 0 and 130 ms, and the probability of evoked spike response in the mPFC measured. We found that BLA input increased vHipp-evoked spike probability at ISIs 40-130 ms, but decreased spike probability at ISIs 10-20 ms. This would be consistent with activation of inhibitory interneurons at shorter ISIs by BLA stimulation. In contrast, in MAM-treated rats BLA stimulation increased vHipp-evoked spike probability in mPFC at all ISIs tested. Given that interneurons are driven primarily by N-methyl-D-aspartate (NMDA) channel activation, the effects of the NMDA channel blocker, phencyclidine (PCP), were tested. PCP was found to completely attenuate the inhibitory effect of BLA input on vHipp-evoked responses in mPFC at shorter ISIs, causing the response in control rats treated with PCP to resemble that observed in the MAM rat. In contrast to the effects of BLA stimulation on vHipp-mPFCevoked responses, there was no inhibitory period when examining the effects of vHipp stimulation on BLA-mPFC-evoked responses in control rats, but in MAM-treated rats there was a significant inhibition at short intervals. Thus, both affective input arising from the BLA and context-dependent input from the vHipp exert a modulatory effect on mPFC neural activity in response to these inputs. Whereas the BLA potentiated vHipp input to the mPFC at long intervals, there was a short-interval inhibitory period that appeared to be mediated by an NMDA-dependent drive of interneurons. This inhibitory modulation was absent in the model of schizophrenia and following PCP, which is consistent with an interneuron disruption in this disorder.

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Section: Modulatory Influence Of Bla On Vhipp-evoked Firing In Mpfc Isupporting

confidence: 85%

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

Esmaeili

Grace

2013

Neuropsychopharmacol

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“…The original finding consistent with a preferential involvement of CA2 showed profound loss of parvalbumin immunoreactivity (a marker of specific subclasses of interneurons) in this subregion [130], replicated in [131,132], although decreases in parvalbumin immunoreactivity outside the hippocampus are widespread [133]. Relative to other hippocampal subfields, binding assays have shown reduced AMPA [134] and histamine H3 receptor binding [135] in CA2 of patients diagnosed with schizophrenia and bipolar disorder respectively , and together these histological and neurochemical abnormalities may manifest as morphological changes at the structural level [136].…”

Section: Box 4: Ca2 In Diseasementioning

confidence: 62%

Updating hippocampal representations: CA2 joins the circuit

Jones

McHugh

2011

Trends in Neurosciences

114

106

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The hippocampus integrates the encoding, storage and recall of memories, binding the spatiotemporal and sensory information that constitutes experience and keeping episodes in their correct context. The rapid and accurate processing of such daunting volumes of continuouslychanging data relies on dynamically assigning different aspects of mnemonic processing to specialized, interconnected networks corresponding to the anatomical subfields of dentate gyrus (DG), CA3 and CA1. However, differentially processed information ultimately has to be reintegrated into conjunctive representations, and this is unlikely to be achieved by unidirectional, sequential steps through a DG-CA3-CA1 loop. In this Review, we highlight recently discovered anatomical and physiological features that are likely to necessitate updates to the hippocampal circuit diagram, particularly by incorporating the oft-neglected CA2 region.3

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“…Our sub-chronic PCP dosing regime causes reduced density of parvalbumin-immunoreactive neurons in hippocampal regions (Abdul-Monim et al, 2007) and levels of brain-derived neurotrophic factor mRNA (BDNF) in cortical regions (Snigdha et al, 2007) in rats. Reductions in GABAergic interneurones in these areas have been found in post-mortem analysis from patients with schizophrenia (Benes et al, 1991;Benes and Berretta, 2001;Beasley et al, 2002;Zhang and Reynolds, 2002). We have shown that atypical but not classical antipsychotics can reverse these cognitive deficits; however, in the clinic there is differing evidence for the efficacy of atypical antipsychotics in improving cognition with the CATIE study (Lieberman, 2006;Keefe et al, 2007) and the UK Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS; Jones et al, 2006; suggesting that antipsychotics actually have a limited effect.…”

Section: Introductionmentioning

confidence: 79%

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

et al. 2009

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A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia

Cited by 427 publications

References 30 publications

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

Updating hippocampal representations: CA2 joins the circuit

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

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