Luis Carrillo-Reid

To move through the world, animals extract visual features from objects. Although visual object encoding is considered a cortical attribute, subcortical areas also contain visual processing circuits. Using electrophysiological recordings of spiny projection neurons (SPNs) located in a target region of the primary visual cortex, we identified striatal modules that process basic visual features. SPNs from the direct and indirect pathways exhibited high orientation selectivity in the absence of behavioral contingencies. SPNs population activity reliably predicted different visual features. Pathway-specific silencing of SPNs revealed that high orientation selectivity depends on intra-striatal connectivity. Thus, specialized striatal modules are active participants in visual feature extraction. These findings indicate parallel visual information processing in basal ganglia circuits, expanding current models of visual perception beyond cortical networks.

Parkinson‘s disease (PD) is a neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons. PD is usually defined by motor deficits such as rest tremor, bradykinesia, and rigidity. Nevertheless, some sensory impairments that may appear before motor dysfunctions or throughout the disease drastically reduce the quality of life of PD patients. PD patients often present difficulties discriminating against basic properties of objects, indicating alterations in visual processing. However, how visual discrimination is affected in animal models of PD remains unknown. The use of L-DOPA continues as the most effective therapy for motor deficits observed in diagnosed PD patients, but little is known about the effect of low doses of L-DOPA on visual discrimination. In the present study, we measured behavioral responses of control and parkinsonian adult male mice trained in a visually guided task. Control mice progressively developed stereotyped behaviors reflecting successful discrimination of Go and No-Go signals, whereas parkinsonian mice were unable to discriminate between different orientations of visual stimuli. Using electrophysiological recordings, we observed diminished visual responses in primary visual cortex of unilaterally dopamine-depleted mice, indicating that alterations of visual information processing could contribute to visual discrimination deficits. Remarkably, parkinsonian mice systemically injected with a low concentration of L-DOPA before each session of the visually guided task partially developed stereotyped behaviors and improved task performance, demonstrating a beneficial effect of L-DOPA. Further experiments are necessary to characterize the role of dopamine in visual discrimination in normal and pathological conditions.

Neuronal ensembles, defined as groups of neurons with coordinated activity, have been proposed as the basic motifs for brain computations such as perception, memory, and movement. This chapter delves into the implementation of Singular Value Decomposition (SVD) applied to similarity maps of neuronal population vectors as an analytical method to identify neuronal ensembles from calcium imaging recordings. At its core, SVD is a mathematical tool that allows the factorization of data matrices. In the context of neuronal ensemble identification, SVD could be applied to similarity maps constructed from multidimensional population vectors, where the dimensionality of the array is defined by the total number of observed neurons; thus similar population vectors are extracted as different SVD factors. Population vectors depict neuronal activity states as screenshots of active and inactive neurons at different time windows. The goal of this chapter is to provide the conceptual intuition for the implementation of SVD from similarity maps to identify neuronal ensembles. The identification of neuronal ensembles could shed light to understand the role of neuronal population dynamics in brain function.

The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release in the hippocampal CA1 region could modulate spatial memory formation. However, the role of hippocampal dopamine increase on weak or strong spatial memories remains unclear. We show that male mice exploring two objects located in a familiar environment for 5 min created a short-term memory (weak) that cannot be retrieved 1 d later, whereas 10 min exploration created a long-term memory (strong) that can be retrieved 1 d later. Remarkably, hippocampal dopamine elevation during the encoding of weak object location memories (OLMs) allowed their retrieval 1 d later but dopamine elevation during the encoding of strong OLMs promoted the preference for a familiar object location over a novel object location after 24 h. Moreover, dopamine uncaging after the encoding of OLMs did not have effect on weak memories whereas on strong memories diminished the exploration of the novel object location. Additionally, hippocampal dopamine elevation during the retrieval of OLMs did not allow the recovery of weak memories and did not affect the retrieval of strong memory traces. Finally, dopamine elevation increased hippocampal theta oscillations, indicating that dopamine promotes the recurrent activation of specific groups of neurons. Our experiments demonstrate that hippocampal dopaminergic modulation during the encoding of OLMs depends on memory strength indicating that hyperdopaminergic levels that enhance weak experiences could compromise the normal storage of strong memories.

Associative learning is crucial for adapting to environmental changes. Interactions among neuronal populations involving the dorso-medial prefrontal cortex (dmPFC) are proposed to regulate associative learning, but how these neuronal populations store and process information about the association remains unclear. Here we developed a pipeline for longitudinal two-photon imaging and computational dissection of neural population activities in male mouse dmPFC during fear-conditioning procedures, enabling us to detect learning-dependent changes in the dmPFC network topology. Using regularized regression methods and graphical modeling, we found that fear conditioning drove dmPFC reorganization to generate a neuronal ensemble encoding conditioned responses (CR) characterized by enhanced internal coactivity, functional connectivity, and association with conditioned stimuli (CS). Importantly, neurons strongly responding to unconditioned stimuli during conditioning subsequently became hubs of this novel associative network for the CS-to-CR transformation. Altogether, we demonstrate learning-dependent dynamic modulation of population coding structured on the activity-dependent formation of the hub network within the dmPFC.

Motor deficits observed in Parkinson’s disease (PD) are caused by the loss of dopaminergic neurons and the subsequent dopamine depletion in different brain areas. The most common therapy to treat motor symptoms for patients with this disorder is the systemic intake of L-DOPA that increases dopamine levels in all the brain, making it difficult to discern the main locus of dopaminergic action in the alleviation of motor control. Caged compounds are molecules with the ability to release neuromodulators locally in temporary controlled conditions using light. In the present study, we measured the turning behavior of unilateral dopamine-depleted mice before and after dopamine uncaging. The optical delivery of dopamine in the striatum of lesioned mice produced contralateral turning behavior that resembled, to a lesser extent, the contralateral turning behavior evoked by a systemic injection of apomorphine. Contralateral turning behavior induced by dopamine uncaging was temporarily tied to the transient elevation of dopamine concentration and was reversed when dopamine decreased to pathological levels. Remarkably, contralateral turning behavior was tuned by changing the power and frequency of light stimulation, opening the possibility to modulate dopamine fluctuations using different light stimulation protocols. Moreover, striatal dopamine uncaging recapitulated the motor effects of a low concentration of systemic L-DOPA, but with better temporal control of dopamine levels. Finally, dopamine uncaging reduced the pathological synchronization of striatal neuronal ensembles that characterize unilateral dopamine-depleted mice. We conclude that optical delivery of dopamine in the striatum resembles the motor effects induced by systemic injection of dopaminergic agonists in unilateral dopamine-depleted mice. Future experiments using this approach could help to elucidate the role of dopamine in different brain nuclei in normal and pathological conditions.

The development of all-optical techniques and analytical tools to visualize and manipulate the activity of identified neuronal ensembles enables the characterization of causal relations between neuronal activity and behavioral states. In this chapter, we review the implementation of simultaneous two-photon imaging and holographic optogenetics in conjunction with population analytical tools to identify and reactivate neuronal ensembles to control a visual-guided behavior.