An organotypic hippocampo-prefrontal co-culture model for studying long-range connectivity and circuit plasticity
- 1Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany
Abstract
The hippocampal projection to the medial prefrontal cortex (mPFC) is a key component of brain networks involved in cognition and emotion. Here, we establish and validate an organotypic entorhino-hippocampo-prefrontal co-culture model that enables experimental investigation of long-range circuit connectivity and plasticity under controlled in vitro conditions. Anatomical tracing, viral labeling, and ultrastructural analyses demonstrate hippocampal axonal projections and synapse formation within the mPFC. Functional connectivity was supported by hippocampal CA1 stimulation, which evoked postsynaptic responses in 90.6% of recorded layer 2/3 mPFC pyramidal neurons. Intrinsic membrane properties and excitatory synaptic transmission were largely preserved across culture configurations. To demonstrate the experimental utility of the model, we examined the effects of selective alveus lesion and global activity blockade. Alveus lesion produced no detectable changes in the examined synaptic or intrinsic properties of mPFC neurons, whereas tetrodotoxin-mediated activity blockade increased miniature excitatory postsynaptic current frequency and reduced membrane capacitance. Together, these findings establish a versatile experimental platform for investigating long-range circuit connectivity and activity-dependent plasticity, with potential applications in mechanistic studies of neuromodulatory interventions.
Related
- Prefrontal cortex resting-state connectivity is moderated by hunger expectations induced by a placebo intervention in healthy female participants.
- Stress-induced dorsal striatal dopamine release is associated with changes in functional connectivity to the prefrontal cortex in nicotine-dependent individuals—a preliminary report
- Effects of dance and music training on the plasticity of the core empathy network: intra- and inter-network connectivity
- Hippocampo-septal inhibitory feedback controls the medial septal circuit as a function of brain state, pyramidal cell activity and movement speed.
- A unified model of short- and long-term plasticity: Effects on network connectivity and information capacity
BibTeX
@misc{stoehr2026organotypic,
title = {{An organotypic hippocampo-prefrontal co-culture model for studying long-range connectivity and circuit plasticity}},
author = {P. Stoehr and G. Grigoryan and M. Lenz and A. Vlachos},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.760475},
url = {https://www.biorxiv.org/content/10.64898/2026.10.20.760475v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - An organotypic hippocampo-prefrontal co-culture model for studying long-range connectivity and circuit plasticity
AU - P. Stoehr
AU - G. Grigoryan
AU - M. Lenz
AU - A. Vlachos
PY - 2026
DA - 2026/10/20
PB - bioRxiv
DO - 10.64898/2026.10.20.760475
UR - https://www.biorxiv.org/content/10.64898/2026.10.20.760475v1
AB - The hippocampal projection to the medial prefrontal cortex (mPFC) is a key component of brain networks involved in cognition and emotion. Here, we establish and validate an organotypic entorhino-hippocampo-prefrontal co-culture model that enables experimental investigation of long-range circuit connectivity and plasticity under controlled in vitro conditions. Anatomical tracing, viral labeling, and ultrastructural analyses demonstrate hippocampal axonal projections and synapse formation within the mPFC. Functional connectivity was supported by hippocampal CA1 stimulation, which evoked postsynaptic responses in 90.6% of recorded layer 2/3 mPFC pyramidal neurons. Intrinsic membrane properties and excitatory synaptic transmission were largely preserved across culture configurations. To demonstrate the experimental utility of the model, we examined the effects of selective alveus lesion and global activity blockade. Alveus lesion produced no detectable changes in the examined synaptic or intrinsic properties of mPFC neurons, whereas tetrodotoxin-mediated activity blockade increased miniature excitatory postsynaptic current frequency and reduced membrane capacitance. Together, these findings establish a versatile experimental platform for investigating long-range circuit connectivity and activity-dependent plasticity, with potential applications in mechanistic studies of neuromodulatory interventions.
ER -