Hippocampal Sequencing Mechanisms Are Disrupted in a Maternal Immune Activation Model of Schizophrenia Risk.

Episodic memory requires information to be stored and recalled in sequential order, and these processes are disrupted in schizophrenia. Hippocampal phase precession and theta sequences are thought to provide a biological mechanism for sequential ordering of experience at timescales suitable for plasticity. These phenomena have not previously been examined in any models of schizophrenia risk. Here, we examine these phenomena in a maternal immune activation (MIA) rodent model. We show that while individual pyramidal cells in the CA1 region continue to precess normally in MIA animals, the starting phase of precession as an animal enters a new place field is considerably more variable in MIA animals than in controls. A critical consequence of this change is a disorganization of the ordered representation of experience via theta sequences. These results provide the first evidence of a biological-level mechanism that, if it occurs in schizophrenia, may explain aspects of disorganized sequential processing that contribute to the cognitive symptoms of the disorder.SIGNIFICANCE STATEMENT Hippocampal phase precession and theta sequences have been proposed as biophysical mechanisms by which the sequential structure of cognition might be ordered. Disturbances of sequential processing have frequently been observed in schizophrenia. Here, we show for the first time that phase precession and theta sequences are disrupted in a maternal immune activation (MIA) model of schizophrenia risk. This is a result of greater variability in the starting phase of precession, indicating that the mechanisms that coordinate precession at the assembly level are disrupted. We propose that this disturbance in phase precession underlies some of the disorganized cognitive symptoms that occur in schizophrenia. These findings could have important preclinical significance for the identification and treatment of schizophrenia risk factors.

The Detection of Spontaneous Venous Pulsation with Smartphone Video Ophthalmoscopy.

PURPOSE: Spontaneous venous pulsation (SVP) has a high negative predictive value for raised intracranial pressure and is a useful sign when assessing patients with headache. The objective was to determine if smartphone-based video ophthalmoscopy can detect SVP. PATIENTS AND METHODS: In total 233 patients and 291 eyes were recruited from the Dunedin Hospital eye clinic from July to November 2018. Patients were examined by a clinician and graded for SVP with a slit lamp and 78 Dioptre lens. Videos were taken with a smartphone ophthalmoscope and graded by two separate clinicians blinded to the slit lamp findings. RESULTS: Only 272 eyes of 215 patients were included, as others failed in the inclusion criteria for overall video quality. Sensitivity was calculated as how likely the presence of SVP on video was indicative of the presence of SVP on slit lamp. Sensitivity was 84.77% for Observer 1, with 128 videos graded as positive for SVP on video ophthalmoscopy of the 151 identified as positive on slit lamp examination. Sensitivity was 76.82% for Observer 2 with 116 videos correctly identified. The false positive rate was calculated as the number of videos graded positive for SVP that had been graded as negative on slit lamp examination. This was 10.74% for observer 1 and 31.40% for observer 2. CONCLUSION: This study demonstrates that SVP is detected by video ophthalmoscopy. This may be a useful triage, telemedicine and referral tool to be used for patients with headache in a primary care setting.

Exposure to complex environments results in more sparse representations of space in the hippocampus.

The neural circuitry mediating sensory and motor representations is adaptively tuned by an animal's interaction with its environment. Similarly, higher order representations such as spatial memories can be modified by exposure to a complex environment (CE), but in this case the changes in brain circuitry that mediate the effect are less well understood. Here, we show that prolonged CE exposure was associated with increased selectivity of CA1 "place cells" to a particular recording arena compared to a social control (SC) group. Furthermore, fewer CA1 and DG neurons in the CE group expressed high levels of Arc protein, a marker of recent activation, following brief exposure to a completely novel environment. The reduced Arc expression was not attributable to overall changes in cell density or number. These data indicate that one effect of CE exposure is to modify high-level spatial representations in the brain by increasing the sparsity of population coding within networks of neurons. Greater sparsity could result in a more efficient and compact coding system that might alter behavioural performance on spatial tasks. The results from a behavioural experiment were consistent with this hypothesis, as CE-treated animals habituated more rapidly to a novel environment despite showing equivalent initial responding.

Behavioural deficits associated with maternal immune activation in the rat model of schizophrenia.

Schizophrenia is associated with changes in memory and contextual processing. As maternal infection is a risk factor in schizophrenia we tested for these impairments in a maternal immune activation (MIA) animal model. MIA rats displayed impaired object recognition memory, despite intact object discrimination, and a reduced reinstatement of rearing in response to a contextual manipulation. These results link MIA to contextual impairments in schizophrenia, possibly through changes in hippocampal function.