SfN 2026: Neural Circuit Research in Neurodegeneration

SfN 2026: Neural Circuit Research in Neurodegeneration

Overview

Neural circuit dysfunction is increasingly recognized as a central mechanism in neurodegenerative diseases, bridging molecular pathology with clinical symptoms. At SfN Neuroscience 2026, the neurodegeneration sessions will feature extensive coverage of circuit-level alterations in Alzheimer's disease (AD), Parkinson's disease (PD), and related disorders. This page catalogs presentations on synaptic dysfunction, circuit remodeling, and network-level changes across the neurodegenerative disease spectrum[@society2026].

This research domain represents a critical translational bridge—understanding how protein aggregates disrupt neural networks provides insight into early cognitive and motor symptoms, while identifying novel therapeutic targets for circuit restoration.

Alzheimer's Disease: Circuit Dysfunction and Network Decline

Synaptic Pathology in AD

The synaptic compartment is a primary target in Alzheimer's disease, with synaptic loss correlating strongest with cognitive decline. SfN 2026 will feature extensive coverage of:

Amyloid-Beta Synaptic Toxicity

• Oligomeric species as the most synaptotoxic forms
• NMDA receptor dysfunction and excitotoxicity
• AMPA receptor trafficking abnormalities
• Synaptic scaffolding protein disruption (PSD95, Homer)
• Presynaptic vesicle cycle impairment

Tau-Mediated Synaptic Dysfunction

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SfN 2026: Neural Circuit Research in Neurodegeneration

Overview

Neural circuit dysfunction is increasingly recognized as a central mechanism in neurodegenerative diseases, bridging molecular pathology with clinical symptoms. At SfN Neuroscience 2026, the neurodegeneration sessions will feature extensive coverage of circuit-level alterations in Alzheimer's disease (AD), Parkinson's disease (PD), and related disorders. This page catalogs presentations on synaptic dysfunction, circuit remodeling, and network-level changes across the neurodegenerative disease spectrum[@society2026].

This research domain represents a critical translational bridge—understanding how protein aggregates disrupt neural networks provides insight into early cognitive and motor symptoms, while identifying novel therapeutic targets for circuit restoration.

Alzheimer's Disease: Circuit Dysfunction and Network Decline

Synaptic Pathology in AD

The synaptic compartment is a primary target in Alzheimer's disease, with synaptic loss correlating strongest with cognitive decline. SfN 2026 will feature extensive coverage of:

Amyloid-Beta Synaptic Toxicity

• Oligomeric species as the most synaptotoxic forms
• NMDA receptor dysfunction and excitotoxicity
• AMPA receptor trafficking abnormalities
• Synaptic scaffolding protein disruption (PSD95, Homer)
• Presynaptic vesicle cycle impairment

Tau-Mediated Synaptic Dysfunction

• Tau spread along synaptic connections
• Dendritic spine loss and remodeling
• Axonal transport disruption
• Synaptic mitochondria dysfunction

Neural Circuit Alterations in AD

Entorhinal-Hippocampal Circuit

The entorhinal cortex-hippocampus circuit is the earliest site of neurodegeneration in AD:

Key presentations will cover:

• EC layer II neuron vulnerability
• Dentate gyrus granule cell loss
• CA1 pyramidal cell dysfunction
• Pattern separation deficits

Cortical-Cortical Networks

• Default mode network disruption
• Salience network alterations
• Frontoparietal network dysfunction
• Cross-network connectivity breakdown

Key Session Topics

| Topic | Focus Area |
|-------|-------------|
| Synaptic Proteomics | Postsynaptic density alterations |
| Network Oscillations | Theta-gamma coupling deficits |
| Dendritic Spines | Spine loss mechanisms and recovery |
| Glial-Neuronal Circuits | Astrocyte and microglia interactions |

Therapeutic Implications

Circuit-level interventions at SfN 2026:

• Deep brain stimulation for memory circuits
• Transcranial magnetic stimulation protocols
• Optogenetic circuit restoration approaches
• Chemogenetic manipulation strategies

Parkinson's Disease: Motor and Non-Motor Circuit Dysfunction

Basal Ganglia Circuit Alterations

The basal ganglia motor circuit is fundamentally disrupted in PD:

PD Pathophysiology:

• Dopaminergic neuron loss in substantia nigra pars compacta
• Striatal dopamine depletion
• Indirect pathway overactivity -> bradykinesia/rigidity
• Hyperdirect pathway facilitation

Dopaminergic Circuit Remodeling

• Nigrostriatal pathway degeneration
• Mesocortical pathway involvement
• Mesolimbic pathway and non-motor symptoms
• Tuberoinfundibular pathway alterations

Non-Motor Circuit Dysfunction

PD extends beyond motor circuits to affect:

Limbic System Circuits

• Amygdala circuitry and emotional processing
• Hippocampal circuits and cognitive impairment
• Orbitofrontal cortex and decision-making

Autonomic Circuits

• Dorsal motor nucleus of vagus involvement
• Enteric nervous system circuits (gut-brain axis)
• Cardiac sympathetic denervation

Key Session Topics

| Topic | Focus Area |
|-------|-------------|
| Basal Ganglia Dynamics | Activity pattern changes in PD |
| Subthalamic Nucleus | STN physiology and DBS targets |
| Pedunculopontine Nucleus | Gait and postural control circuits |
| Cortico-Striatal Loops | Information processing deficits |

Therapeutic Circuit Interventions

• Deep brain stimulation (STN, GPi)
• Levodopa-induced dyskinesias circuit mechanisms
• Cell replacement circuit reconstruction
• Network-level biomarkers

Synaptic Dysfunction: Common Mechanisms

Shared Synaptic Vulnerabilities

Calcium Homeostasis

• Voltage-gated calcium channel dysregulation
• ER calcium store depletion
• Mitochondrial calcium overload
• Synaptic calcium signaling disruption

Oxidative Stress

• Mitochondrial ROS production
• NADPH oxidase activation
• Synaptic antioxidant depletion
• Protein oxidation at synapses

Neuroinflammation

• Microglia-synapse interactions
• Complement-mediated synaptic pruning
• Cytokine effects on synaptic function
• Astrocytic glutamate handling

Protein Aggregation Spread

Network-Level Dysfunction

Oscillatory abnormalities

• Beta band hyperactivity in PD
• Theta-gamma coupling deficits in AD
• Gamma oscillations disruption
• Cross-frequency coupling alterations

Connectivity Changes

| Disease | Network Changes |
|---------|-----------------|
| AD | Default mode network hypoconnectivity |
| PD | Motor network hyperconnectivity |
| FTD | Salience network disruption |
| ALS | Motor network degeneration |

SfN 2026 Presentation Framework

Symposia Categories

• C.02.h-i: Synaptic dysfunction and circuit analysis in AD
• C.03.c-d: Cellular and circuit mechanisms in PD
• C.05: Tauopathies and synucleinopathies circuit effects
• D.01: Neurotoxicity and circuit-level neuroprotection

Poster Session Themes

• Synaptic proteomics and lipidomics
• Circuit-specific neurodegeneration
• Network oscillations in disease models
• Therapeutic circuit modulation

Cross-Linking to NeuroWiki

Related Mechanisms

• [Amyloid Cascade Pathway](/mechanisms/amyloid-cascade-pathway)
• [Tau Pathology Pathway](/mechanisms/tau-pathology-pathway)
• [Alpha-synuclein Aggregation Pathway](/mechanisms/alpha-synuclein-aggregation-pathway)
• [Neuroinflammation in AD/PD/ALS](/mechanisms/neuroinflammation-ad-pd-als)
• [Mitochondrial Dysfunction in Parkinson's Disease](/mechanisms/mitochondrial-dysfunction-parkinsons)

Related Brain Regions

• [Entorhinal Cortex](/brain-regions/entorhinal-cortex)
• [Hippocampus](/brain-regions/hippocampus)
• [Basal Ganglia](/brain-regions/basal-ganglia)
• [Substantia Nigra](/brain-regions/substantia-nigra)
• [Subthalamic Nucleus](cell-types/subthalamic-nucleus)

Related Cell Types

• [Dopaminergic Neurons](/cell-types/dopaminergic-neurons)
• [Cholinergic Neurons](/cell-types/cholinergic-neurons)
• [Microglia](/cell-types/microglia-neuroinflammation)
• [Astrocytes](/entities/astrocytes)

For comprehensive coverage of glial biology sessions:

• [SfN 2026: Glial Biology in Neurodegeneration](/events/sfn-2026/glial-biology) — microglia, astrocytes, oligodendrocytes in AD/PD

Related Diseases

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Dementia with Lewy Bodies](/diseases/dementia-with-lewy-bodies)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)

Program Status

The detailed scientific program for Neuroscience 2026 is expected to be published in spring 2026. This page will be updated with specific session titles, speakers, and abstracts as they become available from SfN.

See Also

• SfN 2026 Main Page
• [SfN 2026: Neurodegeneration Sessions](/events/sfn-2026/neurodegeneration)
• [Alzheimer's Disease Mechanisms](/diseases/alzheimers-disease)
• [Parkinson's Disease Mechanisms](/diseases/parkinsons-disease)

References

Society for Neuroscience, Neuroscience 2026 (2026)