Hippocampal synaptic plasticity as a biological substrate underlying episodic psychosis

Port, Richard L.; Seybold, Kevin S.

doi:10.1016/0006-3223(94)00128-p

Cited by 23 publications

(8 citation statements)

References 75 publications

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“…However, synaptic proteins and their mRNAs could also change without any alterations in density or other morphological indices such as synaptic size or number of vesicles per synapse; for example, they might change as part of a dysfunction or abnormal regulation of the presynaptic terminal and the exocytotic process (see Zhang et al 1998;Takahashi et al 1999;Honer et al 2000;Atwood and Karunanithi 2002;Tarsa and Goda, 2002;Murthy and De Camilli, 2003). This "molecular synaptic pathology" would be essentially congruent with the concept of "aberrant synaptic plasticity", as has been advocated to occur in schizophrenia (Stevens 1992;Keshavan et al 1993;Port and Seybold 1995;McGlashan and Hoffman 2000). Similar considerations concern the nature of dendritic involvement (Law et al, unpublished data).…”

Section: Hippocampal Pathology In Schizophrenia Affects Synapsesmentioning

confidence: 82%

The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications

2004

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This paper puts the case for the hippocampus as being central to the neuropathology and pathophysiology of schizophrenia. The evidence comes from a range of approaches, both in vivo (neuropsychology, structural and functional imaging) and post mortem (histology, morphometry, gene expression, and neurochemistry). Neuropathologically, the main positive findings concern neuronal morphology, organisation, and presynaptic and dendritic parameters. The results are together suggestive of an altered synaptic circuitry or "wiring" within the hippocampus and its extrinsic connections, especially with the prefrontal cortex. These changes plausibly represent the anatomical component of the aberrant functional connectivity that underlies schizophrenia. Glutamatergic pathways are prominently but not exclusively affected. Changes appear somewhat greater in the left hippocampus than the right, and CA1 is relatively uninvolved compared to other subfields. Hippocampal pathology in schizophrenia may be due to genetic factors, aberrant neurodevelopment, and/or abnormal neural plasticity; it is not due to any recognised neurodegenerative process. Hippocampal involvement is likely to be associated with the neuropsychological impairments of schizophrenia rather than with its psychotic symptoms.

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Section: Hippocampal Pathology In Schizophrenia Affects Synapsesmentioning

confidence: 82%

The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications

2004

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“…54 Hippocampal changes in schizophrenics have long been reported [55][56][57] and models involving reduced LTP proposed. 58 Deficits in spatial memory formation have also been observed in schizophrenia. 59 All of this information points towards the disruption of expression of B3GAT1 as the most likely cause for the phenotype observed in this family.…”

Section: Discussionmentioning

confidence: 99%

β-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation

et al. 2003

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We have mapped and sequenced both chromosome breakpoints of a balanced t(6;11)(q14.2;q25) chromosome translocation that segregates with a schizophrenia-like psychosis. Bioinformatics analysis of the regions revealed a number of confirmed and predicted transcripts. No confirmed transcripts are disrupted by either breakpoint. The chromosome 6 breakpoint region is gene poor, the closest transcript being the serotonin receptor 1E (HTR1E) at 625 kb telomeric to the breakpoint. The chromosome 11 breakpoint is situated close to the telomere. The closest gene, b-1,3-glucuronyltransferase (B3GAT1 or GlcAT-P), is 299 kb centromeric to the breakpoint. B3GAT1 is the key enzyme during the biosynthesis of the carbohydrate epitope HNK-1, which is present on a number of cell adhesion molecules important in neurodevelopment. Mice deleted for the B3GAT1 gene show defects in hippocampal long-term potentiation and in spatial memory formation. We propose that the translocation causes a positional effect on B3GAT1, affecting expression levels and making it a plausible candidate for the psychosis found in this family. More generally, regions close to telomeres are highly polymorphic in both sequence and length in the general population and several studies have implicated subtelomeric deletions as a common cause of idiopathic mental retardation. This leads us to the hypothesis that polymorphic or other variation of the 11q telomere may affect the activity of B3GAT1 and be a risk factor for schizophrenia and related psychoses in the general population.

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“…Episodic psychosis has also been linked to the hippocampus, possibly through processes involving long-term potentiation (e.g. Port and Seybold 1995). Because the effects of HAL in schizophrenia have generally been related to changes in positive symptoms of the disorder (Crow et al 1978), the alterations in hippocampal function produced by HAL may attenuate the ability of sensory input to evoke an associated response leading to a reduction in positive symptoms of schizophrenia.…”

Section: Discussionmentioning

confidence: 98%

“…Autopsy and neuroimaging studies have reported hippocampal abnormalities in cell number and organization in schizophrenics (Altshuler et al 1990;Bogerts et al 1990;Suddath et al 1990;Conrad et al 1991;Arnold et al 1995). Behavioral evidence of hippocampal abnormalities include episodic psychosis (Seidman 1983;Port and Seybold 1995), deficient sensorimotor gating (Swerdlow et al 1994), disrupted association of sensory input to stored material (Hemsley 1994), and disrupted selective attention (Nuechterlein et al 1994). The rabbit classical eyeblink conditioning paradigm may be useful for understanding the role of the hippocampus in schizophrenia.…”

Section: Introductionmentioning

confidence: 97%

Effects of haloperidol on sensory processing in the hippocampus during classical eyeblink conditioning

Sears

Steinmetz

1997

Psychopharmacology

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The rabbit classical eyeblink conditioning paradigm was used to assess the effects of haloperidol on hippocampal function. Haloperidol disrupted hippocampal activity and conditioned responses (CRs) at low but not high conditioned stimulus (CS) intensities. The observed relationship of hippocampal activity and the CR suggested that the hippocampus encoded sensory features associated with the learned response. Sensory processing by the hippocampus appeared to be altered by haloperidol through attenuation of the ability of a CS to evoke a learned response. Results are discussed in terms of the role of the hippocampus in sensory processing and possible mechanisms for the beneficial effects of haloperidol in schizophrenia. Classical eyeblink conditioning may provide a model system for studying behavioral and biological issues relevant to the etiology and treatment of schizophrenia.

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Hippocampal synaptic plasticity as a biological substrate underlying episodic psychosis

Cited by 23 publications

References 75 publications

The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications

The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications

β-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation

Effects of haloperidol on sensory processing in the hippocampus during classical eyeblink conditioning

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