Segregated fronto-cortical and midbrain connections in the mouse and their relation to approach and avoidance orienting behaviors

Abstract

The orchestration of orienting behaviors requires the interaction of many cortical and subcortical areas, for example the superior colliculus (SC), as well as prefrontal areas responsible for top-down control. Orienting involves different behaviors, such as approach and avoidance. In the rat, these behaviors are at least partially mapped onto different SC subdomains, the lateral (SCl) and medial (SCm), respectively. To delineate the circuitry involved in the two types of orienting behavior in mice, we injected retrograde tracer into the intermediate and deep layers of the SCm and SCl, and thereby determined the main input structures to these subdomains. Overall the SCm receives larger numbers of afferents compared to the SCl. The prefrontal cingulate area (Cg), visual, oculomotor, and auditory areas provide strong input to the SCm, while prefrontal motor area 2 (M2), and somatosensory areas provide strong input to the SCl. The prefrontal areas Cg and M2 in turn connect to different cortical and subcortical areas, as determined by anterograde tract tracing. Even though connectivity pattern often overlap, our labeling approaches identified segregated neural circuits involving SCm, Cg, secondary visual cortices, auditory areas, and the dysgranular retrospenial cortex likely to be involved in avoidance behaviors. Conversely, SCl, M2, somatosensory cortex, and the granular retrospenial cortex comprise a network likely involved in approach/appetitive behaviors.

Keywords: RRID:SCR_013672; approach behaviors; avoidance behaviors; cingulate area; motor cortex area 2; superior colliculus.

Figure 1

Retrograde tracer injections in the superior colliculus. (a) Photomicrograph of fluorogold injection into the medial superior colliculus. (b) Photomicrograph of fluorogold injection into the lateral superior colliculus. All scale bars equate to 250 µm. (c) Summary of injections. Each shaded area represents the extent of the labeled injection site for both medial and lateral SC conditions. The darker shading indicates overlap of injection volume. Nomenclature in this and all others figures is derived from Franklin, K.B.J. & Paxinos, G. 2012. For abbreviations see list

Figure 2

Summary of average percentage of total labeled cells for ipsilateral brain areas after injections of fluorogold into the medial (gray) and lateral (black) superior colliculus. Error bars represent 95% confidence intervals

Figure 3

Summary of average percentage of total labeled cells for contralateral brain areas after injections of fluorogold into the medial (gray) and lateral (black) superior colliculus. Error bars represent 95% confidence intervals

Figure 4

Example photomicrographs of retrogradely labeled brain areas after injection of fluorogold into the medial superior colliculus. (a) Labeling seen in the secondary visual cortex (V2MM/V2ML). (b) Labeling seen in the primary auditory cortex (Au1). (c) Labeling seen in the dysgranular retrospenial cortex (RSD). (d) Labeling seen in the cingulate area (Cg) and motor cortex area 2 (M2). (e) Labeling seen in the ventromedial substantia nigra (SNR[vm]). (f) Labeling seen in the dorsolateral zona incerta (ZI). All scale bars equate to 250 µm

Figure 5

Example photomicrographs of retrogradely labeled brain areas after injection of fluorogold into the lateral superior colliculus. (a) Labeling seen in the primary somatosensory area (S1BF). (b) Labeling seen in the primary motor cortex (M1). (c) Labeling seen in the granular retrospenial cortex (RSG). (d) Labeling seen in the Cg and M2. (e) Labeling seen in the dorsolateral SNR. (f) Labeling seen in the ventromedial ZI. All scale bars equate to 250 µm

Figure 6

Modulation indices (MIs) for tracing data. (a) MIs of retrograde labeling in M2 versus Cg (left) and SNR(dl) versus SNR(vm) (right). (b) MIs of anterograde labeling in SCm versus SCl (left) and CPu(dm) versus CPu(dl) (right). White bars indicate MIs after SCm injections, black bars indicate MIs after SCl injections, gray bars indicate MIs after M2 injections, and dashed bars MIs after Cg injections) “*”represents p < .02

Figure 7

Connectivity matrix summary of SCm, SCl retrograde connections, and of Cg, and M2 anterograde connections. Connectivity is displayed in four levels, low, medium, high and very high, indicated by line thickness. Areas highlighted in colored boxes are those which receive input from the frontal cortex and also send projections to the relevant SC subdivision. Proportion of the box highlighted illustrates the strength of connection from the respective frontal area

Figure 8

Injections sites for anterograde tracing. (a) Photomicrograph of biotinylated dextran anime injection into the M2. (b) Photomicrograph of biotinylated dextran amine injection into the Cg. All scale bars equate to 250 µm. (c) Summary of injection sites for all cases in the anterograde tracing in the Cg and M2. Each shaded area represents the extent of the labeled injection site for both the Cg and M2. The darker shading indicates overlap of injection volume

Figure 9

Example photomicrographs of anterogradely labeled brain areas after injection of BDA into the M2. (a) Labeling seen in the primary somatosensory area (S1BF). (b) Labeling seen throughout the RSD, M2, primary motor cortex (M1) and S1. (c) Labeling seen in the lateral portion of the superior colliculus (SCl). (d) Labeling seen in the dorsolateral striatum (CPu[dl]). (e) Labeling seen in the thalamus, namely the lateral posterior mediorostral and laterorostral part (LPLR, LPMR), the mediodorsal (MDL), the central lateral (CL) and the posterior (Po). All scale bars equate to 250 µm

Figure 10

Example photomicrographs of anterogradely labeled brain areas after injection of BDA into the cingulate area. (a) Labeling seen in the secondary visual cortex (V2MM, V2ML). (b) Labeling seen throughout the RSD, RSG. (c) Labeling seen in the medial portion of the superior colliculus (SCm). (d) Labeling seen in the dorsomedial striatum (CPu[dm]). (e) Labeling seen in the thalamus, namely the LPMR, the MDL, the CL and the Po and the lateral habenula (LHb). All scale bars equate to 250 µm