Abstract
The modulation of sensory processing by attention is a key feature of cognition. Much of the previous work on attention has been carried out in non-human primates. The primate visual system is hierarchically organised, and the intensity of attentional modulation has been found to be greater higher up in the hierarchy. The mapping of attention effects across mouse higher visual areas is unknown. Here I have recorded from 7 visual cortical areas whilst mice performed a cross-modal attention switching task. I found that primary visual cortex (V1) was the area most strongly modulated by attention, an inversion of the pattern expected from analogy to primate data. Although there has been a great deal of excellent work into attention, its neural circuit basis is poorly understood. I used all-optical methods to investigate whether two molecularly defined interneuron types are involved in the attentional modulation of visual stimulus selectivity in mouse V1 - vasoactive intestinal peptide expressing (VIP) and parvalbumin expressing (PV) interneurons.First, VIP interneurons exert disinhibitory control over pyramidal neurons through inhibition of somatostatin expressing (SOM) interneurons. This disinhibitory motif is a candidate mechanism for the changes in neural activity with attention. I bi-directionally manipulated the activity of VIP interneurons as mice performed an attention switching task. I recorded the activity of VIP, SOM, PV interneurons and pyramidal neurons identified in the same tissue and found that while both attention and VIP manipulation affected the activity in all 4 cell classes, their effects on the stimulus selectivity of the neural population were orthogonal. In support of their independence, attention and VIP-SOM disinhibition produced distinct patterns of changes in activity and different changes in the noise correlations between and within the 4 recorded cell classes. Collectively, these experiments provide evidence against a role for VIP interneurons in the neural correlates of cross-modal attention and highlight the ability of cortical circuits to simultaneously contain multiple strong non-interacting modulations in the same neural population.
Second, PV interneurons are strongly modulated by attention and exert a powerful influence on the activity of cortical circuits. I optogenetically excited PV interneurons whilst recording activity in V1 of mice performing the same cross-modal attention switching task. The effects of PV activation had opposite effects on the network depending on the cognitive state of the animal. Strengths of PV activation which inhibited non-PV visually evoked activity during calibration sessions elicited no-change or an increase in non-PV activity when the mouse viewed the same visual stimuli during the attention switching task. Additionally, activation of PV interneurons modified stimulus selectivity in an attention dependent manner. However, interpretation of these results is made difficult because monotonic changes in stimulus selectivity depend on non-monotonic and paradoxical changes in the activity of non-PV cells with increasing PV photoactivation. Further work is required to identify the causes and implications of these unexpected effects, but they suggest caution when interpreting the effects of perturbing interneuron activity.
| Date of Award | 1 Jul 2023 |
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| Original language | English |
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| Supervisor | Adil Khan (Supervisor) & Juan Burrone (Supervisor) |