Biology subjects

Nietz, A. K.

Publications and source records attributed to Nietz, A. K..

3 recordsLinked to original sources

bioRxiv2024

Cortex-wide characterization of decision-making neural dynamics during spatial navigation

Decision-making during freely moving behaviors involves complex interactions among many cortical and subcortical regions. However, the spatiotemporal coordination across regions to generate a decision is less understood. Using a head-mounted widefield microscope, cortex-wide calcium dynamics were recorded in mice expressing GCaMP7f as they navigated an 8-maze using two paradigms. The first was an alternating pattern that required short term memory of the previous trial to make the correct decision and the second after a rule change to a fixed path in which rewards were delivered only on the left side. Identification of cortex-wide activation states revealed differences between the two paradigms. There was a higher probability for a visual/retrosplenial cortical state during the alternating paradigm and higher probability of a secondary motor and posterior parietal state during left-only. Three state sequences (motifs) illustrated both anterior and posterior activity propagations across the cortex. The anterior propagating motifs had the highest probability around the decision and posterior propagating motifs peaked following the decision. The latter, likely reflecting internal feedback to influence future actions, were more common in the left-only paradigm. Therefore, the probabilities and sequences of cortical states differ when working memory is required versus a fixed trajectory reward paradigm.

neuroscience↗

bioRxiv2024

Cerebral cortical functional hyperconnectivity in a mouse model of spinocerebellar ataxia type 8 (SCA8)

Spinocerebellar Ataxia Type 8 (SCA8) is an inherited neurodegenerative disease caused by a bidirectionally expressed CTG[bullet]CAG expansion mutation in the ATXN-8 and ATXN8-OS genes. While primarily a motor disorder, psychiatric and cognitive symptoms have been reported. It is difficult to elucidate how the disease alters brain function in areas with little or no degeneration producing both motor and cognitive symptoms. Using transparent polymer skulls and CNS-wide GCaMP6f expression, we studied neocortical networks throughout SCA8 progression using wide-field Ca2+ imaging in a transgenic mouse model of SCA8. We observed that neocortical networks in SCA8+ mice were hyperconnected globally which led to network configurations with increased global efficiency and centrality. At the regional level, significant network changes occurred in nearly all cortical regions, however mainly involved sensory and association cortices. Changes in functional connectivity in anterior motor regions worsened later in the disease. Near perfect decoding of animal genotype was obtained using a generalized linear model based on canonical correlation strengths between activity in cortical regions. The major contributors to decoding were concentrated in the somatosensory, higher visual and retrosplenial cortices and occasionally extended into the motor regions, demonstrating that the areas with the largest network changes are predictive of disease state.

molecular biology↗

bioRxiv2022

To be and not to be: Wide-field Ca2+ imaging reveals neocortical functional segmentation combines stability and flexibility

The stability and flexibility of the functional parcellation of the cerebral cortex is fundamental to how familiar and novel information is both represented and stored. We leveraged new advances in Ca2+ sensors and microscopy to understand the dynamics of functional segmentation in the dorsal cerebral cortex. We performed wide-field Ca2+ imaging in head-fixed mice and used spatial Independent Component Analysis (ICA) to identify independent spatial sources of Ca2+ fluorescence. The imaging data were evaluated over multiple timescales and discrete behaviors including resting, walking, and grooming. When evaluated over the entire dataset, a set of template independent components (ICs) were identified that were common across behaviors. Template ICs were present across a range of timescales, from days to 30 seconds, although with lower occurrence probability at shorter timescales, highlighting the stability of the functional segmentation. Importantly, unique ICs emerged at the shorter duration timescales that could act to transiently refine the cortical network. When data were evaluated by behavior, both common and behavior-specific ICs emerged. Each behavior is composed of unique combinations of common and behavior-specific ICs. These observations suggest that cerebral cortical functional segmentation exhibits considerable spatial stability over time and behaviors while retaining the flexibility for task-dependent reorganization.

neuroscience↗