Unsupervised Phenotyping Reveals Disrupted Neural Firing Characteristics in the Anterior Thalamus and Surrounding Brain Regions Following Third-Trimester Equivalent Alcohol Exposure in Mice
Acute binge-like third-trimester-equivalent alcohol exposure (TTAE) causes apoptosic neurodegeneration in brain regions necessary for spatial learning and memory, such as the anterior thalamus (AT), which encodes context-relevant information, including head direction. While we are beginning to understand the behavioral consequences of this exposure, the neural correlates of spatial cognition deficits are underexplored. Thus, we recorded a mixture of neurons from the AT and surrounding brain regions in mice with TTAE while they freely moved within a controlled environment. To model acute binge-like TTAE, C57BL/6J mice received 2 injections of 2.5 g/kg alcohol (or saline) on post-natal day (PND) 7. Subjects were then left undisturbed until the day of surgery as adults (>PND 60), when they were implanted with silicon or multi-wire arrays. Mice were placed in a circular 40 cm diameter arena under dim red light with 2 LED cues on the walls that rotated on a pseudo-random basis while electrophysiological data was recorded. Following data preprocessing, spike and waveform features were extracted from each putative single spiking unit. These features were reduced utilizing uniform manifold approximation and projection (UMAP). Following dimensionality reduction, we used agglomerative hierarchical clustering to find populations of neurons with similar features. Following this, we compared each feature based on treatment and found the features most important to disambiguate TTAEs impact on neural activity. TTAE was associated with decreases in mean firing rate, peak firing rate, rebound index, and tail decay constant, increases in alpha, peak to trough time, and repolarization time, and bidirectional differences as a function of neuronal subtype in burst index and rebound index. This suggests that TTAE produces long-lasting and fundamental differences in spiking features that can be observed in vivo and are amenable to intervention. Together, this dataset provides further clarifying criteria that can be utilized to diagnose and treat FASD.