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Goltstein, P. M.

Publications and source records attributed to Goltstein, P. M..

5 recordsLinked to original sources

Sensorimotor remapping drives task specialization in prefrontal cortex

The prefrontal cortex (PFC) plays a key role in flexible, context-dependent decision-making. Yet, the population-level mechanisms that support this flexibility remain unclear: is there a generalist neural population involved in representing useful information across tasks, or are representations distributed over multiple modules of task-specialized subpopulations? Here, we investigate whether the population structure modularity in medial prefrontal cortex (mPFC) increases with sensorimotor remapping between task rules in two different paradigms. In a paradigm where all stimuli were remapped, we found a highly modular structure with two task-specialized subpopulations and one generalist. In a different paradigm where only half of the stimuli were remapped, modularity decreased but remained significant. Based on predictions drawn from a recurrent neural network fitted to experimental data, we propose that a gain modulation by global inhibition of mPFC can explain how task-specialized neurons emerge to varying degrees in each paradigm.

neuroscience↗

Ocular dominance columns in mouse visual cortex

The columnar organization of response properties is a fundamental feature of the mammalian visual cortex. However, columns have not been observed universally across all mammalian species. Here, we report the discovery of ocular dominance columns in mouse visual cortex. Our observation in this minute cortical area sets a new boundary condition for models explaining the emergence of columnar organizations in the neocortex.

neuroscience↗

Spaced training enhances memory and prefrontal ensemble stability in mice.

Memory is substantially improved when learning is distributed over time, an effect called "spacing effect". So far it has not been studied how spaced learning affects neuronal ensembles presumably underlying memory. In the present study, we investigate whether trial spacing increases the stability or size of neuronal ensembles. Mice were trained in the "everyday memory" task, an appetitive, naturalistic, delayed matching-to-place task. Spacing trials by 60 minutes produced more robust memories than training with shorter or longer intervals. c-Fos labeling and chemogenetic inactivation established the necessity of the dorsomedial prefrontal cortex (dmPFC) for successful memory storage. In vivo calcium imaging of excitatory dmPFC neurons revealed that longer trial spacing increased the similarity of the population activity pattern on subsequent encoding trials and upon retrieval. Conversely, trial spacing did not affect the size of the total neuronal ensemble or the size of subpopulations dedicated to specific task-related behaviors and events. Thus, spaced learning promotes reactivation of prefrontal neuronal ensembles processing episodic-like memories.

neuroscience↗

Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

Alzheimers disease (AD) is associated with aberrant neuronal activity levels. How those activity alterations emerge and how stable they are over time in vivo, however, remains elusive to date. To address these questions we chronically recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice and their non-transgenic littermates over the course of 4 weeks by means of calcium imaging. Surprisingly, aberrant neuronal activity was very stable over time. Moreover, we identified a slow progressive gain of activity of former intermediately active neurons as the main source of new highly active neurons. Interestingly, fluctuations in neuronal activity were independent from amyloid plaque proximity, but aberrant activity levels were more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in AD patients is the consequence of stable single cell aberrant neuronal activity, a finding of potential therapeutic relevance.\n\nO_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC=\"FIGDIR/small/801902v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@16f8461org.highwire.dtl.DTLVardef@5c0952org.highwire.dtl.DTLVardef@681c04org.highwire.dtl.DTLVardef@107854a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Benchmarking miniaturized microscopy against two-photon calcium imaging using single-cell orientation tuning in mouse visual cortex

Miniaturized microscopes are lightweight imaging devices that allow optical recordings from neurons in freely moving animals over the course of weeks. Despite their ubiquitous use, individual neuronal responses measured with these microscopes have not been directly compared to those obtained with established in vivo imaging techniques such as bench-top two-photon microscopes. To achieve this, we performed calcium imaging in mouse primary visual cortex while presenting animals with drifting gratings. We identified the same neurons in image stacks acquired with both microscopy methods and quantified orientation tuning of individual neurons. The response amplitude and signal-to-noise ratio of calcium transients recorded upon visual stimulation were highly correlated between both microscopy methods, although influenced by neuropil contamination in miniaturized microscopy. Tuning properties, calculated for individual orientation tuned neurons, were strongly correlated between imaging techniques. Thus, neuronal tuning features measured with a miniaturized microscope are quantitatively similar to those obtained with a two-photon microscope.

neuroscience↗