Stackman Jr., Robert W.

While the thalamus and hippocampus are generally understood to contribute to mammalian spatial navigation, the degree to which thalamic input contributes to representations of space during navigation remains unclear. Specifically, anterior dorsal thalamic nuclei (ADN) provide a relational or directional framework known as the head direction (HD) network, which is hypothesized to play a significant role in guiding hippocampal-dependent navigation. The current study focuses on the contribution of the ADN to direction and place-dependent spatial navigation in adult male C57BL6J mice. An inhibitory chemogenetic (hM4Di) receptor was bilaterally expressed in the ADN after viral stereotaxic injection. Mice were trained in a spatially focused task, the Morris water maze (MWM), and after systemic administration of the hM4Di agonist, clozapine-Noxide (CNO) at 5mg/kg, demonstrated equivalent preference for using directional or place-based search behavior. These results suggest that the selective silencing of ADN at 5mg/kg CNO does not negatively affect spatial navigation in mice.

Long-term memories are encoded within the hippocampus, but some are quickly forgotten. Brief exposure of mice to a novel context following encoding of object memory significantly enhances consolidation of the object memory. The memory-enhancing effect of post-training novelty may rely on locus coeruleus tyrosine-hydroxylase expressing neurons which co-release norepinephrine and dopamine in the hippocampus. To test the contribution of norepinephrine to this novelty effect, mice received propranolol, a synthetic beta-adrenergic receptor antagonist (10 mg/kg), to block norepinephrine or 0.9% saline as a control post-training. Pre-novel context exposure and object memory was tested 24 hr later. Results revealed that propranolol did not block the memory enhancing effect of post-training novel context exposure. Further, the memory performance of the propranolol-treated mice was comparable to that of saline-treated mice. These findings support the view that enhanced consolidation of object memory brought about by post-training novel context exposure is not dependent upon norepinephrine neurotransmission.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that effects about 1 in 44 children and has steadily increased in prevalence over the last decades. ASD is characterized by the diagnostic criteria of a persistent deficit in social communication and interaction and restricted or repetitive behaviors. The amygdala plays an essential role in regulating these behaviors and has continuously been shown to be affected in patients with ASD. As the amygdala is connected throughout the brain with cortical and subcortical areas, it is crucial to understand potential circuit impairments that contribute to the development and progression of behavioral characteristics. In this study, we investigated the role of ASD-associated TBR1 haploinsufficiency on morphological and functional amygdala connectivity. While we don’t see differences in inputs to the basal amygdala (BA), we demonstrated a difference in the BA to prefrontal cortex (PFC) pathway. Interestingly, we show a specific innervation difference of layer 5 neurons in the infralimbic (IL) but not prelimbic (PL) nuclei in the PFC. In accordance with the overall reduced density of BA axons in the IL, we show a decreased density of excitatory synapses. To investigate possible functional consequences of this projection deficit, we characterized pre-and postsynaptic functions of BA-PFC synapses. TBR1 haploinsufficiency impairs the postsynaptic function of BA-PL layer 2/3 and IL layer 5 synapses. BA-PL layer 2/3 synapses show an increased AMPA/NMDA receptor ratio, while this is not observed in BA-IL layer 5 synapses. However, TBR1 haploinsufficiency increases the AMPA and NMDA receptor-mediated currents at these synapses, further highlighting that BA-PL and BA-IL synapses are different and that partial loss of TBR1 affects circuits differently. This novel characterization of the consequences of a TBR1 haploinsufficiency on BA connectivity contributes to the critical understanding of this ASD-associated gene and its detrimental effects that contribute to the underlying behavioral phenotype.

Previous research revealed that episodic memories are more likely to be consolidated if something novel occurs in relative temporal proximity to the original learned event (Dunsmoor, Murty, Davachi, & Phelps, 2015). Further, research conducted with rodents has revealed that novel contextual exposure following encoding of a spatial memory in a food-motivated task results in enhanced consolidation of that spatial memory (Takeuchi, Duszkiewics, Sonneborn et al., 2016). The present study sought to examine the influence of novel context exposure on non-spatial object memory in adult female and male C57BL/6J mice when novel context exposure follows encoding of object memory under two memory strength training protocols. Results revealed that regardless of memory strength or gender, subjects exposed to a novel context following encoding of object memory exhibited greater exploration of the novel object when assessed 23.5 h later. Thus, novel context exposure significantly enhanced the consolidation of recently encoded object memory. As novel context exposure has been shown to increase dopamine release in the hippocampus, these results are consistent with the theory of synaptic tag and capture, whereby activated dopaminergic afferents enhance the on-going consolidation of non-spatial object memory. Future studies will entail parsing potential neurotransmitter modulatory afferents via pharmacological antagonists.