Biology subjects

Haesler, S.

Publications and source records attributed to Haesler, S..

5 recordsLinked to original sources

bioRxiv2025

Behavioral orienting but not novelty activates dopamine neurons

Novel stimuli have a profound impact on brain function and behavior. They evoke attention, arousal and sensory exploration and induce synaptic plasticity in brain regions related to learning and memory. Many of these effects have been attributed to novelty-evoked activation of the dopaminergic midbrain and dopamine (DA) release in major projection targets in the striatum. However, it remains controversial if individual DA neurons respond to novel stimuli. To address this question, we recorded and manipulated DA neurons in mice exposed to novel and familiar odors while monitoring orienting behaviors including exploratory sniffing, facial movements, and pupil dilation. We found that DA neurons were activated by orienting behaviors, rather than by novelty itself. Moreover, their activity was causally involved in generating the orienting responses. Finally, we identified a major input region to the dopaminergic midbrain which couples orienting to DA firing. Activity in the mediodorsal pons (mdPons) correlated tightly with sniffing and facial movements. Consequently, optogenetic stimulation of glutamatergic mdPons neurons induced both orienting and DA firing. Our findings suggest that DA neurons do not respond to novelty per se but are activated through descending glutamatergic projections from the mdPons. This mechanism links salient sensory events to DA release, providing a basis for novelty-evoked exploration and plasticity.

neuroscience↗

bioRxiv2025

The anterior olfactory nucleus mediates curious exploration evoked by novel odors

The spontaneous exploratory reaction to novel stimuli reflects a fundamental form of curiosity, which is widely observed in the animal kingdom. How sensory systems mediate the recognition of novel stimuli to evoke exploration is not well understood. To address this question, we presented novel and familiar olfactory stimuli to head-restrained mice, while measuring novelty-evoked exploratory behaviors. In parallel, we recorded neural activity in primary olfactory cortical structures, the anterior olfactory nucleus (AON) or the anterior piriform cortex (aPCx). Novelty strongly modulated odor responses in the AON, but only weakly in the aPCx. Pharmacological and chemogenetic inactivation of the AON but not the aPCx disrupted exploratory responses. During long-term habituation over multiple days, sensory representations were drifting in the AON whereas they became stable within one day in the aPCx. Our findings suggest that AON and aPCx play distinct roles in novelty-evoked exploration. While the AON mediates the immediate reaction to novel stimuli, the aPCx exhibits stable stimulus representations, consistent with supporting odor memory.

neuroscience↗

bioRxiv2024

Experience shapes the transformation of olfactory representations along the cortico-hippocampal pathway

Perception relies on the neural representation of sensory stimuli. Primary sensory cortical representations have been extensively studied, but how sensory information propagates to memory-related multisensory areas has not been well described. We studied this question in the olfactory cortico-hippocampal pathway in mice. We recorded single units in the anterior olfactory nucleus (AON), the anterior piriform cortex (aPCx), lateral entorhinal cortex (LEC), the hippocampal CA1 subfield, and the subiculum (SUB) while animals performed a non-associative learning paradigm involving novel and familiar stimuli. In the AON, neurons were broadly tuned to different chemicals, and their responses were strongly modulated by experience. From the AON to hippocampal structures, the selectivity of neurons for specific odorants increased, concurrent with the development of population-level odor representations, which became independent of novelty and familiarity. While both stimulus identity and experience were thus reflected in all regions, their neural representations progressively separated. Our findings provide a potential mechanism for how sensory representations are transformed to support stimulus identification and implicit memories.

neuroscience↗

bioRxiv2023

Microfluidic interfaces for chronic bidirectional access to the brain.

AO_SCPLOWBSTRACTC_SCPLOWHere, we used micron-scale 3D printing to develop microfluidic interfaces which provide chronic fluidic access to the brain of preclinical research models. In mice, we show the delivery interface enables faster, more precise and physiologically less disruptive fluid injection. Moreover, we demonstrate the blood brain barrier (BBB) is intact after chronic implantation of the sampling interface and establish frequent, longitudinal sampling of CSF and biomarkers from the ventricle over long time periods of up to 200 days.

neuroscience↗

bioRxiv2020

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

To study the dynamics of neural processing across timescales, we require the ability to follow the spiking of thousands of individually separable neurons over weeks and months, during unrestrained behavior. To address this need, we introduce the Neuropixels 2.0 probe together with novel analysis algorithms. The new probe has over 5,000 sites and is miniaturized such that two probes plus a headstage, recording 768 sites at once, weigh just over 1 g, suitable for implanting chronically in small mammals. Recordings with high quality signals persisting for at least two months were reliably obtained in two species and six different labs. Improved site density and arrangement combined with new data processing methods enable automatic post-hoc stabilization of data despite brain movements during behavior and across days, allowing recording from the same neurons in the mouse visual cortex for over 2 months. Additionally, an optional configuration allows for recording from multiple sites per available channel, with a penalty to signal-to-noise ratio. These probes and algorithms enable stable recordings from >10,000 sites during free behavior in small animals such as mice.

neuroscience↗