Preserved navigation abilities and spatio-temporal memory in individuals with autism spectrum disorder.

Cerebellar abnormalities have been reported in autism spectrum disorder (ASD). Beyond its role in hallmark features of ASD, the cerebellum and its connectivity with forebrain structures also play a role in navigation. However, the current understanding of navigation abilities in ASD is equivocal, as is the impact of the disorder on the functional anatomy of the cerebellum. In the present study, we investigated the navigation behavior of a population of ASD and typically developing (TD) adults related to their brain anatomy as assessed by structural and functional MRI at rest. We used the Starmaze task, which permits assessing and distinguishing two complex navigation behaviors, one based on allocentric learning and the other on egocentric learning of a route with multiple decision points. Compared to TD controls, individuals with ASD showed similar exploration, learning, and strategy performance and preference. In addition, there was no difference in the structural or functional anatomy of the cerebellar circuits involved in navigation between the two groups. The findings of our work suggest that navigation abilities, spatio-temporal memory, and their underlying circuits are preserved in individuals with ASD.

Anatomical and physiological foundations of cerebello-hippocampal interaction.

Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde transneuronal tracer in mice, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally suggest that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6-12 Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.

Author Correction: A hippocampo-cerebellar centred network for the learning and execution of sequence-based navigation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A hippocampo-cerebellar centred network for the learning and execution of sequence-based navigation.

How do we translate self-motion into goal-directed actions? Here we investigate the cognitive architecture underlying self-motion processing during exploration and goal-directed behaviour. The task, performed in an environment with limited and ambiguous external landmarks, constrained mice to use self-motion based information for sequence-based navigation. The post-behavioural analysis combined brain network characterization based on c-Fos imaging and graph theory analysis as well as computational modelling of the learning process. The study revealed a widespread network centred around the cerebral cortex and basal ganglia during the exploration phase, while a network dominated by hippocampal and cerebellar activity appeared to sustain sequence-based navigation. The learning process could be modelled by an algorithm combining memory of past actions and model-free reinforcement learning, which parameters pointed toward a central role of hippocampal and cerebellar structures for learning to translate self-motion into a sequence of goal-directed actions.

Complementary Roles of the Hippocampus and the Dorsomedial Striatum during Spatial and Sequence-Based Navigation Behavior.

We investigated the neural bases of navigation based on spatial or sequential egocentric representation during the completion of the starmaze, a complex goal-directed navigation task. In this maze, mice had to swim along a path composed of three choice points to find a hidden platform. As reported previously, this task can be solved by using two hippocampal-dependent strategies encoded in parallel i) the allocentric strategy requiring encoding of the contextual information, and ii) the sequential egocentric strategy requiring temporal encoding of a sequence of successive body movements associated to specific choice points. Mice were trained during one day and tested the following day in a single probe trial to reveal which of the two strategies was spontaneously preferred by each animal. Imaging of the activity-dependent gene c-fos revealed that both strategies are supported by an overlapping network involving the dorsal hippocampus, the dorsomedial striatum (DMS) and the medial prefrontal cortex. A significant higher activation of the ventral CA1 subregion was observed when mice used the sequential egocentric strategy. To investigate the potential different roles of the dorsal hippocampus and the DMS in both types of navigation, we performed region-specific excitotoxic lesions of each of these two structures. Dorsal hippocampus lesioned mice were unable to optimally learn the sequence but improved their performances by developing a serial strategy instead. DMS lesioned mice were severely impaired, failing to learn the task. Our data support the view that the hippocampus organizes information into a spatio-temporal representation, which can then be used by the DMS to perform goal-directed navigation.

Effect of exposure to 1,800 MHz electromagnetic fields on heat shock proteins and glial cells in the brain of developing rats.

The increasing use of mobile phones by children raise issues about the effects of electromagnetic fields (EMF) on the immature Central Nervous System (CNS). In the present study, we quantified cell stress and glial responses in the brain of developing rats one day after a single exposure of 2 h to a GSM 1,800 MHz signal at a brain average Specific Absorption Rate (SAR) in the range of 1.7 to 2.5 W/kg. Young rats, exposed to EMF on postnatal days (P) 5 (n = 6), 15 (n = 5) or 35 (n = 6), were compared to pseudo-exposed littermate rats (n = 6 at all ages). We used western blotting to detect heat shock proteins (HSPs) and cytoskeleton- or neurotransmission-related proteins in the developing astroglia. The GSM signal had no significant effect on the abundance of HSP60, HSC70 or HSP90, of serine racemase, glutamate transporters including GLT1 and GLAST, or of glial fibrillary acid protein (GFAP) in either total or soluble tissue extracts. Imunohistochemical detection of CD68 antigen in brain sections from pseudo-exposed and exposed animals did not reveal any differences in the morphology or distribution of microglial cells. These results provide no evidence for acute cell stress or glial reactions indicative of early neural cell damage, in developing brains exposed to 1,800 MHz signals in the range of SAR used in our study.