Characterization of Feedback Neurons in the High-Level Visual Cortical Areas That Project Directly to the Primary Visual Cortex in the Cat

Abstract

Previous studies indicate that top-down influence plays a critical role in visual information processing and perceptual detection. However, the substrate that carries top-down influence remains poorly understood. Using a combined technique of retrograde neuronal tracing and immunofluorescent double labeling, we characterized the distribution and cell type of feedback neurons in cat’s high-level visual cortical areas that send direct connections to the primary visual cortex (V1: area 17). Our results showed: (1) the high-level visual cortex of area 21a at the ventral stream and PMLS area at the dorsal stream have a similar proportion of feedback neurons back projecting to the V1 area, (2) the distribution of feedback neurons in the higher-order visual area 21a and PMLS was significantly denser than in the intermediate visual cortex of area 19 and 18, (3) feedback neurons in all observed high-level visual cortex were found in layer II–III, IV, V, and VI, with a higher proportion in layer II–III, V, and VI than in layer IV, and (4) most feedback neurons were CaMKII-positive excitatory neurons, and few of them were identified as inhibitory GABAergic neurons. These results may argue against the segregation of ventral and dorsal streams during visual information processing, and support “reverse hierarchy theory” or interactive model proposing that recurrent connections between V1 and higher-order visual areas constitute the functional circuits that mediate visual perception. Also, the corticocortical feedback neurons from high-level visual cortical areas to the V1 area are mostly excitatory in nature.

Suppression of top-down influence decreases neuronal excitability and contrast sensitivity in the V1 cortex of cat

“…In conclusion, our results suggest that suppression of top-down influence with c-tDCS in A7 decreases neuronal activity in the V1 cortex, which is consistent with some of previous studies using neural imaging measurement 6 , 12 and some single-unit recording studies that report facilitatory top-down effects on most neurons in the V1 or low-level visual cortex 7 , 9 , 33 , 41 , and is also supported by neuronal tracing studies that identify most feedback neurons as excitatory cells 43 , 44 although top-down modulation may mediated by a mechanism of disinhibition 41 . Our result is opposite to the results of other studies that report inhibitory top-down effects of V2/V3 cortex on V1 neurons in primate and mouse 8 , 29 , 32 .…”

“…Some authors report top-down facilitation effect on the late-phase neuronal response 41 or late ERP components (90–140 ms) 38 , whereas others find a strong attentional modulation on the initial response of VEP component (57 ms) and population response during the first wave of visual processing (< 100 ms) in the human V1 cortex 39 , 40 . It is likely that the top-down effect on the initial and late response components in the V1 may depend on the strength of top-down influence during different tasks 39 or the source of top-down connections from different cortical areas to the V1 cortex 42 , 43 or types of visual signals such as figure-ground stimuli 41 . Considering that A7 has a weblike and direct projections to the V1 10 , 12 , and tDCS manipulation may trigger a large scale of top-down influence from A7, it could be reasonable that visual stimulation with full-screen size gratings may potentiate a drastic top-down effect on VEPs, even the initial VEP components, in the V1 as observed in this study.…”

“…After VEPs recording, the cat’s brain tissue was harvested and used for histological study according to methods described previously 43 . Briefly, the cat was deeply anesthetized with ketamine HCl (80 mg/kg, im) and then transcardially perfused with 0.9% saline followed by 2% paraformaldehyde in 0.1 M phosphate buffered saline (PBS).…”

Effects of top-down influence suppression on behavioral and V1 neuronal contrast sensitivity functions in cats

“…Our results suggest that the normal top-down influence of A7 in the absence of c-tDCS enhances neuronal activity in V1, consistent with previous studies in neuroimaging ( Chen et al., 2014 ; Galuske et al., 2002 ; Huang et al., 2004 ; Liang et al., 2007 ; Tong et al., 2011 ; Yang et al., 2016b ) and single-unit recordings ( Huh et al., 2018 ; Jansen-Amorim et al., 2012 ; Wang et al., 2000 , 2007 , 2010 ; Zhang et al., 2014 ). Our results are also supported by neuronal tracing studies that showed that most feedback neurons are CaMKII-positive pyramidal neurons ( Budd, 1998 ; Han et al., 2008 ; Johnson and Burkhalter, 1994 , 1997 ; Pan et al., 2021b ) and may use primarily excitatory amino acid as neurotransmitters ( Johnson and Burkhalter, 1994 ; van Loon et al., 2015 ). The observed excitatory top-down influence of A7 on V1 is, however, different from reports of inhibitory top-down effects of V2/V3 on V1 neurons in primate and rodent studies ( Hishida et al., 2019 ; Maniglia et al., 2019 ; Nassi et al., 2013 , 2014 ).…”

“…The results suggest that top-down influence of A7 affects both early and later responses in V1, consistent with some previous studies ( Foster et al., 2021 ; Kelly and Mohr, 2018 ; Zhang et al., 2015 ), but inconsistent with other studies that report top-down effects only on the later responses in V1 ( Alilović et al., 2019 ; Baumgartner et al., 2018 ; Kirchberger et al., 2021 ). Future studies are necessary to clarify if top-down effects on the early and late response components in V1 depend on the strength of the top-down influence in different tasks ( Kelly and Mohr, 2018 ; Slotnick, 2018 ) or the source of top-down influence ( Johnson and Burkhalter, 1997 ; Pan et al., 2021b ). We found that behavioral contrast detection is more highly coupled to early sensory responses in V1, which is consistent with previous observations ( Bao et al., 2010 ; Richter et al., 2018 ; Zhang et al., 2015 ).…”