Scott Alpizar

Nerve terminals generally engage in two opposite and essential forms of synaptic plasticity (facilitation or depression) that play critical roles in learning and memory. While the molecular components of both types of terminals are similar with regards to vesicle fusion, much less is known about their molecular control of electrical signaling. Measurements of the electrical impulses (action potentials) underlying these two forms of plasticity have been difficult in small nerve terminals due to… Show more

Nerve terminals generally engage in two opposite and essential forms of synaptic plasticity (facilitation or depression) that play critical roles in learning and memory. While the molecular components of both types of terminals are similar with regards to vesicle fusion, much less is known about their molecular control of electrical signaling. Measurements of the electrical impulses (action potentials) underlying these two forms of plasticity have been difficult in small nerve terminals due to their size. In this study we deployed optical physiology measurements to overcome this size barrier. Here, we identify a unique mechanism (Kvβ1 subunit) that enables broadening of the presynaptic action potentials that selectively supports synaptic facilitation, but does not alter any other aspects of nerve terminal function. Show less

Ion channels are microscopic pore proteins in the membrane that open and close in response to chemical and electrical stimuli. This simple concept underlies rapid electrical signaling in the brain as well as several important aspects of neural plasticity. Although the soma accounts for less than 1% of many neurons by membrane area, it has been the major site of measuring ion channel function. However, the axon is one of the longest processes found in cellular biology and hosts a multitude of… Show more

Ion channels are microscopic pore proteins in the membrane that open and close in response to chemical and electrical stimuli. This simple concept underlies rapid electrical signaling in the brain as well as several important aspects of neural plasticity. Although the soma accounts for less than 1% of many neurons by membrane area, it has been the major site of measuring ion channel function. However, the axon is one of the longest processes found in cellular biology and hosts a multitude of critical signaling functions in the brain. Not only does the axon initiate and rapidly propagate action potentials (APs) across the brain but it also forms the presynaptic terminals that convert these electrical inputs into chemical outputs. Here, we review recent advances in the physiological role of ion channels within the diverse landscape of the axon and presynaptic terminals. Show less

The axon initial segment (AIS) is a specialized region within the proximal portion of the axon that initiates action potentials thanks in large part to an enrichment of sodium channels. The scaffolding protein ankyrinG (AnkG) is essential for the recruitment of sodium channels as well as several other intracellular and extracellular proteins to the AIS. In the present study, we explore the role of the cell adhesion molecule (CAM) neurofascin-186 (NF-186) in arranging the individual molecular… Show more

The axon initial segment (AIS) is a specialized region within the proximal portion of the axon that initiates action potentials thanks in large part to an enrichment of sodium channels. The scaffolding protein ankyrinG (AnkG) is essential for the recruitment of sodium channels as well as several other intracellular and extracellular proteins to the AIS. In the present study, we explore the role of the cell adhesion molecule (CAM) neurofascin-186 (NF-186) in arranging the individual molecular components of the AIS in cultured rat hippocampal neurons. Using a CRISPR depletion strategy to ablate NF expression, we found that the loss of NF selectively perturbed AnkG accumulation and its relative proximal distribution within the AIS. We found that the overexpression of sodium channels could restore AnkG accumulation, but not its altered distribution within the AIS without NF present. We go on to show that although the loss of NF altered AnkG distribution, sodium channel function within the AIS remained normal. Taken together, these results demonstrate that the regulation of AnkG and sodium channel accumulation within the AIS can occur independently of one another, potentially mediated by other binding partners such as NF. Show less