Janelle M.P. Pakan's Lab
Institution: Otto-von-Guericke-Universität Magdeburg
Featured research (5)
The retrosplenial cortex (RSC) has diverse functional inputs and is engaged by various sensory, spatial, and associative learning tasks. We examine how multiple functional aspects are integrated on the single-cell level in the RSC and how the encoding of task-related parameters changes across learning. Using a visuospatial context discrimination paradigm and two-photon calcium imaging in behaving mice, a large proportion of dysgranular RSC neurons was found to encode multiple task-related dimensions while forming context-value associations across learning. During reversal learning requiring increased cognitive flexibility, we revealed an increased proportion of multidimensional encoding neurons that showed higher decoding accuracy for behaviorally relevant context-value associations. Chemogenetic inactivation of RSC led to decreased behavioral context discrimination during learning phases in which context-value associations were formed, while recall of previously formed associations remained intact. RSC inactivation resulted in a persistent positive behavioral bias in valuing contexts, indicating a role for the RSC in context-value updating.
The primary visual cortex has the capacity to store stimulus-specific information locally. A new study reveals a direct role for the hippocampus in experience-dependent cortical plasticity when visual stimuli are presented in a predictable temporal order.
As we move through the environment we experience constantly changing sensory input that must be merged with our ongoing motor behaviors - creating dynamic interactions between our sensory and motor systems. Active behaviors such as locomotion generally increase the sensory-evoked neuronal activity in visual and somatosensory cortices, but evidence suggests that locomotion largely suppresses neuronal responses in the auditory cortex. However, whether this effect is ubiquitous across different anatomical regions of the auditory cortex is largely unknown. In mice, auditory association fields such as the dorsal auditory cortex (AuD), have been shown to have different physiological response properties, protein expression patterns, and cortical as well as subcortical connections, in comparison to primary auditory regions (A1) - suggesting there may be important functional differences. Here we examined locomotion-related modulation of neuronal activity in cortical layers ⅔ of AuD and A1 using two-photon Ca2+ imaging in head-fixed behaving mice that are able to freely run on a spherical treadmill. We determined the proportion of neurons in these two auditory regions that show enhanced and suppressed sensory-evoked responses during locomotion and quantified the depth of modulation. We found that A1 shows more suppression and AuD more enhanced responses during locomotion periods. We further revealed differences in the circuitry between these auditory regions and motor cortex, and found that AuD is more highly connected to motor cortical regions. Finally, we compared the cell-type specific locomotion-evoked modulation of responses in AuD and found that, while subpopulations of PV-expressing interneurons showed heterogeneous responses, the population in general was largely suppressed during locomotion, while excitatory population responses were generally enhanced in AuD. Therefore, neurons in primary and dorsal auditory fields have distinct response properties, with dorsal regions exhibiting enhanced activity in response to movement. This functional distinction may be important for auditory processing during navigation and acoustically guided behavior.
The cerebral cortex and cerebellum both play important roles in sensorimotor processing, however, precise connections between these major brain structures remain elusive. Using anterograde mono-trans-synaptic tracing, we elucidate cerebrocerebellar pathways originating from primary motor, sensory, and association cortex. We confirm a highly organized topography of corticopontine projections in mice; however, we found no corticopontine projections originating from primary auditory cortex and detail several potential extra-pontine cerebrocerebellar pathways. The cerebellar hemispheres were the major target of resulting disynaptic mossy fiber terminals, but we also found at least sparse cerebrocerebellar projections to every lobule of the cerebellum. Notably, projections originating from association cortex resulted in less laterality than primary sensory/motor cortices. Within molecularly defined cerebellar modules we found spatial overlap of mossy fiber terminals, originating from functionally distinct cortical areas, within crus I, paraflocculus, and vermal regions IV/V and VI-highlighting these regions as potential hubs for multimodal cortical influence.
The potential for neuronal representations of external stimuli to be modified by previous experience is critical for efficient sensory processing and improved behavioral outcomes. To investigate how repeated exposure to a visual stimulus affects its representation in mouse primary visual cortex (V1), we performed two-photon calcium imaging of layer 2/3 neurons and assessed responses before, during, and after the presentation of a repetitive stimulus over 5 consecutive days. We found a stimulus-specific enhancement of the neuronal representation of the repetitively presented stimulus when it was associated with a reward. This was observed both after mice actively learned a rewarded task and when the reward was randomly received. Stimulus-specific enhanced representation resulted both from neurons gaining selectivity and from increased response reliability in previously selective neurons. In the absence of reward, there was either no change in stimulus representation or a decreased representation when the stimulus was viewed at a fixed temporal frequency. Pairing a second stimulus with a reward led to a similar enhanced representation and increased discriminability between the equally rewarded stimuli. Single-neuron responses showed that separate subpopulations discriminated between the two rewarded stimuli depending on whether the stimuli were displayed in a virtual environment or viewed on a single screen. We suggest that reward-associated responses enable the generalization of enhanced stimulus representation across these V1 subpopulations. We propose that this dynamic regulation of visual processing based on the behavioral relevance of sensory input ultimately enhances and stabilizes the representation of task-relevant features while suppressing responses to non-relevant stimuli.