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Seminars

Two talks on electrophysiological studies of brain neurons

Students Josiah Sinclair and Jonathan Wong, Professors Loren Haarsma (Physics) and Paul Moes (Psychology)
Tuesday, April 30, at 3:45 p.m. in SB110.

Electrophysiological evidence for normal proportions of inhibitory (GABA) intra-hemispheric synaptic connections following abnormal development of corpus callosum axons

Josiah Sinclair

Agenesis of the corpus callosum (AgCC) occurs in humans and mice when growing axons fail to cross the midline to connect left and right cortical areas. These misguided fibers form bilateral pathways, known as Probst Bundles (PB’s), which run anterior-to-posterior near the medial cortical surface. AgCC symptoms overlap with autism-spectrum disorder traits, but researchers have speculated that individuals with PB’s, have less severe symptoms than those without. Previous research has established that the axons of the PB fibers conduct action potentials, but no studies have determined if PB fibers make functional connections with layer V pyramidal cells. The present study used electrical stimulation of PB axons in mouse brain slices and patch-clamp electrophysiology to examine the existence of inhibitory post-synaptic currents (e.g., GABA-mediated responses) in cortical cells, and to examine the location and nature of these inhibitory responses. As with normal corpus callosum pathway stimulation, stimulation of PB axons produced very few GABA-mediated responses in layer V pyramidal cells. Together with other outcomes from the present study, the low number of GABA-mediated responses suggests that the resulting intra-hemispheric connections mirror normal inter-hemispheric connections, despite their abnormal growth patterns.

Electrophysiological evidence for normal excitatory intra-hemispheric synaptic connections following abnormal development of corpus callosum axons

Jonathan Wong

Agenesis of the corpus callosum (AgCC) occurs in humans and mice when developing axons fail to cross the midline to connect left and right cortical areas. These misguided fibers form bilateral pathways, known as Probst Bundles (PB’s), which run anterior-to-posterior near the medial cortical surface. AgCC symptoms overlap with autism-spectrum disorder traits, but researchers have speculated that individuals with PB’s, have fewer symptoms than those without. Previous research has established that the axons of the PB fibers conduct action potentials, but no studies have determined if PB fibers make functional connections with layer V pyramidal cells. The present study used electrical stimulation of PB axons in mouse brain slices and patch-clamp electrophysiology to verify the existence of mono-synaptic connections to cortical cells from PB axons, and to examine the location and nature of excitatory post-synaptic currents. Results verified the existence of functional excitatory mono-synaptic responses in layer V pyramidal cells following stimulation of PB’s and surrounding intra-cortical tissue rostral to the target cell – similar to responses seen with normal corpus callosum stimulation. Significantly fewer monosynaptic excitatory responses were identified when stimulating caudally to the target cell confirming that the heterotypical pathways are established in an anterior-to-posterior direction. The existence a large number of mono-synaptic excitatory responses from intra-cortical stimulation (in addition to PB stimulation) suggests that many of the anterior-to-posterior fibers travel outside of PB. These results confirm that PB fibers make functional intra-hemispheric connections to layer V pyramidal cells that mirror the properties of normal inter-hemispheric synaptic connections.


 

 



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