THE ROLE OF THE HPC-PFC PATHWAY AND SCHEMA MECHANISMS IN

PSYCHIATRIC DISEASES

By Siobhan Campbell

Honours Neuroscience Dissertation- Library Project

Introduction

The HPC-PFC Pathway:vHPC vmPFC

The Stress Response - HPA

Walker et al. (2008)

MRs/GRsHPC/PFC

Hypothesis

The HPC-PFC pathway is damaged by stress, disrupting neural function and cognition in psychiatric disease

Outline

Schema

Pathway

Stress & Structure

Stress & Function

Cognition & Disease

Cognition in Disease - Schemas

• Previous knowledge networks• Increase rate of consolidation• Facilitate decision-making• Built upon HPC-PFC interactions

Lewis et al. (2011)

History of ResearchTract-Tracing

1977 – 1995 Electrophysiology

1996 – 2000 Lesions

2004 – 2011

The HPC-PFC

Pathway

Lesions Disrupt Oscillations

vHPC lesions reduces oscillations in vmPFC

Brockmann et al. (2011)

Brain Oscillations

Lewis et al. (2011)

Stress Disrupts Oscillations

Oliveria et al. (2013)

Stress Disrupts Structure

vHPC vPFC @ Layer2

• Stress affects pathway input

• PFC atrophy

Cerqueria et al. (2007)

Stress Disrupts Function@HPC-PFC synapses

LTP memory traces

@CA1 synapses

Booth et al. (2014)

Cerqueria et al. (2007)

Memory in Disease - Depression@HPC-PFC synapses:Stress impairs LTPAntidepressants restore LTP

Rocher et al. (2004)

Memory in Disease - Schizophrenia

Suh et al. (2013)

Memory in Disease - Schizophrenia

Sigurdsson et al. (2010)

Pathway in Disease - Schema

ACC/PrL: • schema• decision-making• stress

Conclusion:Pathway damage could prevent activation of schemas

Tse et al. (2011)

SummaryThe HPC-PFC pathway:1. Exists2. Interacts with stress and disease3. Is involved in creating and updating

schemas

Hypothesis:The HPC-PFC pathway is damaged by stress, disrupting neural function and cognition in psychiatric disease.

Future StudiesSchema & Schizophrenia

Animals - Tse et al. (2007) Humans – Van Kesteren et al. (2010)

Author: Siobhan CampbellSupervisor: Lisa Genzel

Morris LabCCNS

1 George Sq.Edinburgh