Anterior Commissure Regulates Neuronal Activity of Amygdalae and Influences Locomotor Activity, Social Interaction and Fear Memory in Mice

Abstract

The two hemispheres of the vertebrate brain are connected through several commissures. Although the anterior commissure (AC) is the most conserved white matter structure in the brains of different vertebrates, its complete physiological functionality remains elusive. Since the AC is involved in the connection between two amygdalae and because amygdalae are critical for emotional behaviors and social interaction, we assessed amygdalar activity and function to investigate the physiological role of the AC. We first performed ex vivo electrophysiological recording on mouse brains to demonstrate that the AC delivers a positive signal to facilitate synaptic responses and to recruit basolateral amygdalar neurons via glutamatergic synapses. Transection was then undertaken to investigate the role of the AC in vivo. Results from in vivo optogenetic stimulation suggest that AC transection impairs mutual activation between two basolateral amygdalae. Behavioral analyses were then used to assess if AC surgical lesioning results in hyperactivity, anxiety, social reduction or learning/memory impairment, which are behavioral features associated with neuropsychiatric disorders, such as autism spectrum disorders. We found that AC transection results in higher locomotor activity, aberrant social interaction and reduced associative memory, but not anxiety. Moreover, systemic administration of D-cycloserine, a coagonist of N-methyl-D-aspartate receptor, ameliorated auditory fear memory in AC-transected mice, reinforcing our evidence that the AC potentiates the activity of basolateral amygdalae. Our study suggests that the AC regulates basolateral amygdalar activity and influences neuropsychiatry-related behaviors in mice.

White Matter Dissection of the Fetal Brain

“…The anterior commissure's functional implications in humans are still somewhat elusive, appearing to be related to olfactory and non-visual interhemispheric communication (Gerrish et al, 2014). Studies on mice have found that the transection of this fascicle results in higher motor activity, aberrant social interaction and reduced associative memory, behavioral features associated with neuropsychiatric disorders, such as autism spectrum disorders (Hsu et al, 2020). The uncinate fasciculus is reported to contribute to reward/punishment based learning (Von Der Heide et al, 2013), facial emotional processing (Coad et al, 2017), emotional empathy (Oishi et al, 2015), and self-regulation (Passamonti et al, 2012).…”

Delta-Frequency Augmentation and Synchronization in Seizure Discharges and Telencephalic Transmission

“…The highly coherent behavioral manifestations also lend a strong support for the imperativeness of delta oscillations, which serve as the basic or natural frequencies of the telencephalic networks. It is of note that MD, prelimbic cortex, and contralateral BLA ( Figure 7 ) are all telencephalic structures receiving direct glutamatergic input from left BLA ( McDonald, 1987 , Mátyás et al., 2014 , Hintiryan et al, 2019 ; Huang et al., 2019 ; Hsu et al., 2020 ). In contrast to the potential role of INs in local spreading (see above), PN probably is essential for distant or long-range projection of the oscillating activities.…”

Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1+/− mouse model of autism spectrum disorders

“…An additional challenge will be determining whether ASD diagnosis can precede the therapeutic window in humans. Also, the effects of dietary zinc supplementation on neural circuits other than the thalamic-LA projection pathway such as the olfactory system and anterior commissure-related interhemispheric connectivity that have previously been shown to be dysfunctional in Tbr1 +/− mice [ 15 , 38 , 39 ], or those that may underlie ASD-associated behaviours observed in Tbr1 +/− mice (i.e. prefrontal cortex and ventral hippocampus for social memory and behaviours) require examination in future studies.…”