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Klee, J. L.

Publications and source records attributed to Klee, J. L..

4 recordsLinked to original sources

Internal and external contexts drive distinct dynamics in shared action-encoding striatal neurons

Animals can initiate movements either in response to external cues or from internal drive, yet how the brain flexibly supports both remains unclear. Disorders such as Parkinsons disease disrupt these modes differently, suggesting distinct underlying mechanisms. Such differences could arise from specialized circuits dedicated to each action mode or from shared neuronal populations that shift their dynamics across contexts. To distinguish between these possibilities, we performed two-photon calcium imaging in the dorsolateral striatum as mice executed the same lever press either spontaneously or in response to a cue, enabling direct comparison of internally and externally triggered actions. Unsupervised clustering revealed subpopulations of neurons modulated during cue, movement, or post-action periods. Critically, the same neurons were tuned to movement across initiation contexts. However, the dynamics of this shared population evolved within distinct "context" and "action" subspaces, even before movement initiation. Both dopamine D1- and D2-receptor-expressing spiny projection neurons contributed to both subspaces, with D1-SPNs more active at the time of the sensory stimulus. These results show that context shapes neural dynamics within a shared movement-encoding population, revealing a context-generalizable striatal code that supports flexible movement initiation across internal and external drives.

neuroscience↗

Coexisting persistent and dynamic representations of stimulus, time and trial outcome emerge in the hippocampus-prefrontal circuitry during learning of a temporal association

Temporal associations between sensory stimuli separated in time rely on the interaction between the hippocampus and medial prefrontal cortex (mPFC). However, it is not known how changes in their neural activity support the emergence of temporal association learning. Here, we use simultaneous electrophysiological recordings in the hippocampal CA1 region and mPFC of mice to elucidate the neural dynamics underlying memory formation in an auditory trace conditioning task. We found that in both areas conditioned (CS+/CS-) and unconditioned stimuli (US) evoked similar temporal sequences of neural responses that progressively diverged during learning. Additionally, persistent CS representations emerged in mPFC after learning, supported by CS+ coding states whose transient reactivation reliably predicted lick onset and behavioral performance on single trials. These results show that coordination of temporal sequences in CA1 and persistent activity in mPFC may underlie temporal association learning, and that transient reactivations of engrams in mPFC predict the animal behavior. HighlightsO_LITemporal representation of CS+, but not CS- and US, strengthens in CA1 after learning. C_LIO_LISimilarity between stimulus and reward temporal representations decrease with learning, but is recovered in error trials. C_LIO_LIRepresentation of stimulus identity is strong and stable in PFC since stimulus onset, while it only emerges in CA1 during trace period. C_LIO_LINeural states defined on faster time-scales reveal the emergence of CS coding states in PFC whose onset predicts lick times and task performance. C_LIO_LIPFC-CA1 states do not increase coordination during late CS+ stimulus and trace. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/497926v2_fig0.gif" ALT="Figure 0"> View larger version (32K): org.highwire.dtl.DTLVardef@93f7a7org.highwire.dtl.DTLVardef@6804a0org.highwire.dtl.DTLVardef@107a6a2org.highwire.dtl.DTLVardef@14cfb23_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 0:C_FLOATNO Graphical Abstract C_FIG

neuroscience↗

Learning differentially shapes prefrontal and hippocampal activity patterns during classical conditioning

The ability to use sensory cues to inform goal directed actions is a critical component of intelligent behavior. To study how sound cues are translated into anticipatory licking during classical appetitive conditioning, we employed high-density electrophysiological recordings from the hippocampal CA1 area and the prefrontal cortex (PFC). CA1 and PFC neurons undergo distinct learning dependent changes at the single cell level and maintain representations of cue identity during anticipatory behavior at the population level. In addition, reactivation of task-related neuronal assemblies during hippocampal awake Sharp-Wave Ripples (aSWR) changed within individual sessions in CA1 and over the course of multiple sessions in PFC. Despite both areas being highly engaged and synchronized during the task, we found no evidence for coordinated single cell or assembly activity during conditioning trials or aSWR.

neuroscience↗

Reduced firing rates of pyramidal cells in frontal cortex of APP/PS1 can be restored by acute treatment with levetiracetam

In recent years aberrant neural oscillations in various cortical areas have emerged as a common physiological hallmark across mouse models of amyloid pathology and patients with Alzheimers disease. However, much less is known about the underlying effect of amyloid pathology on single cell activity. Here, we used high density silicon probe recordings from frontal cortex area of 9 months old APP/PS1 mice to show that resting state Local Field Potential (LFP) power in the theta and beta band is increased in transgenic animals, while single cell firing rates, specifically of putative pyramidal cells, are significantly reduced. At the same time, these sparsely firing pyramidal cells phase-lock their spiking activity more strongly to the ongoing theta and beta rhythms. Furthermore, we demonstrated that the anti-epileptic drug, levetiracetam, can restore principal cell firing rates back to control levels. Overall, our results highlight reduced firing rates of cortical pyramidal cells as a symptom of amyloid pathology and indicate that lifting cortical inhibition might contribute to the beneficial effects of levetiracetam on AD patients.\n\nO_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

neuroscience↗