Comparison of (stereotactic) parcellations in mouse prefrontal cortex

Abstract

This study compares the cytoarchitectonic parcellation of the prefrontal cortex (PFC) in the mouse as presented in publications that are commonly used for identifying brain areas. Agreement was found to be greater for boundaries in the medial PFC than in the lateral PFC and lowest for those in the orbital areas of the PFC. In this review, we explain and illustrate in a selected series of photographs and stereotactic pictures the differences in location and terminology of the different prefrontal cortical areas. The significance of cytoarchitectonic parcellation is discussed.

Appendices

Appendix 1: Characteristics

Cytoarchitectonic characteristics of boundaries (Van de Werd et al. 2010).

Medial prefrontal subareas anterior to the corpus callosum

Boundary Fr1/Fr2 (frontal areas 1 and 2)

Columns are seen in both Fr1 (frontal area 1) and Fr2 (frontal area 2), but more prominent and more densely packed in Fr2. The columns regard the layers V and VI, but in Fr1 the arrangement of cells in the layer VI might be horizontal instead of columnar.

The size of the cells of the columns is larger in Fr1 than in Fr2.

The layer V rises gradually in Fr1 to reach its most superficial level at the transition from Fr1 to Fr2. This is due to the progressive loss of cells in the layer IV of Fr1 as it approaches the agranular Fr2.

The layer II shows clefts in Fr1, but in Fr2 the layer II cells join into a smooth, less interrupted layer.

Boundary Fr2/ACd (dorsal anterior cingulate area)

Columns are seen in both areas in the layers V and VI, but they are more densely packed in ACd (dorsal anterior cingulate area) than in Fr2.

The size of the cells of the columns is smaller in ACd than in Fr2.

In the layer II of Fr2 the most superficial cells show a smooth surface with layer I, in ACd the cells of the layer II are very much concentrated on its surface, which is irregular.

Boundary ACd/PL (prelimbic area)

Columns are visible in ACd, not in PL. The layer VI in ACd is part of the columnar structure seen in the layers V and VI of that area, but in PL the cells of the layer V are not arranged in a recognizable structure and the cells of its layer VI are arranged in horizontal lines, parallel to the pial surface.

The layer V shows columns in ACd, but not in PL. The cells of the layer V in PL are, however, densely packed. The cells of layer V are larger in PL than in ACd.

The cells of the layer III in ACd are less densely packed than the cells of the layer III in PL. The layer II in ACd is narrow, its cells are concentrated on its surface, in PL the layer II is broader and its cells are spread more equally over the whole layer.

Anterior to the fornix minor of the corpus callosum the deeper layers of the PFC are not visible and the features of layer II and less so of layer III will then be the decisive factors in positioning the boundary.

Boundary PLd/PLv (the dorsal and ventral part of PL)

In the prelimbic area (PL) we distinguish a dorsal part PLd and a ventral part PLv.

The layers V and VI are more densely packed in the ventral than in the dorsal part of PL. The basic structure of these layers remains, however, the same for the ventral as well as the dorsal part of PL.

In both PLd and PLv, the cells of the layer III are less densely packed than in the neighboring layers. As a result the layer III is lighter in appearance in both parts of PL. The layer II is narrower and more densely packed in PLd than in PLv, where the layer is broader and the cells are less densely packed.

Boundary PL/MO (medial orbital area)

In the most frontal part of the PFC PL borders MO, due to absence of the infralimbic area (IL) at that level. The main characteristic of the boundary between PL and medial orbital area (MO) is the equally dispersed cells of the layer II in MO in contrast to the unequal spread of cells in the layer II in PL.

Layer III separates layer II and V more clearly in PL than in MO.

Boundary PL/IL (infralimbic area)

The layers II, III and V are well distinguishable from each other in PL, but in the infralimbic area (IL) they are homogeneous. Some cells of the layer II of IL spread into the layer I, but not in PL or much less so. The cells in layers II-V are smaller in IL than in PL.

The contrast between the clearly distinguishable layer III in PL and the homogeneity of this layer with the neighboring layers in IL is often the easiest sign to determine the boundary between the two areas.

It should be noted that the homogeneity of the layers II, III and V is not always complete in IL as sometimes the layer II might be still distinguishable from the other layers. The layer VI shows a horizontal arrangement of its cells in both PL and IL (infralimbic area).

Boundary IL/MO

The boundary between the infralimbic area (IL) and the medial orbital area (MO) is characterized mainly by the difference in layer II which is homogeneous with the layers III and V and with spreading of cells of the layer II into layer I in IL, while in MO layer II has a sharp border to the layer III.

The cells of the layer II are very equally dispersed in MO, but less so in IL. The cells of layer II are smaller in IL than in MO.

Boundary MO/VO (ventral orbital area)

The boundary between the medial orbital (MO) and ventral orbital (VO) area is determined mainly by layers I-III. Generally the layer II of the medial orbital area (MO) is sharply separated from the layers I and III and the cells in it are rather equally dispersed. In the ventral orbital area (VO), the cells of layer II tend to spread into the layer I and the cells in this layer are less densely packed than in MO. Also some clustering is present in the layer II in VO. The layer III in MO may show fine columns, the layer III in VO usually does not.

Medial subareas caudally to the genu of the corpus callosum

Boundary ACd/ACv (ventral anterior cingulate area)

Columns are seen in ACd but not in ACv (ventral anterior cingulate area).

The cells of the layer VI in ACd are part of the characteristic columnar structure of that area, but the cells of the layer VI in ACv are arranged in horizontal lines.

The cells of the layer V are arranged in columns in ACd, but not in ACv. The cells of the layer V are densely packed in ACv, not in ACd.

In both ACd and ACv, the layer III is easily distinguishable from the neighboring layers by its light appearance.

The layer II of ACd is narrow and its cells are irregularly concentrated on its surface while in ACv the layer II is broader and the cells are spread more equally.

Boundary ACvd/ACvv

In ACv a dorsal part (ACvd) and a ventral part (ACvv) are distinguished.

In all layers, the cells are more densely packed in the ventral than in the dorsal part of ACv. In both ACvd and ACvv, the layer III has a light appearance due to the fact that its cells are less densely packed than in the neighboring layers.

The layer II is narrower and more concentrated in ACvd than in the broader layer II of ACvv.

Difference between PL and ACv

The contrast of the layer III with the neighboring layers is clearer in ACv than in PL. As a consequence the difference between the areas ACd and ACv is less than between the areas ACd and PL. The border between the layers II and I is sharper in ACv than in PL.

Ventral PFC subareas

The ventral areas are known as the ventral orbital (VO), the ventrolateral orbital (VLO) and the lateral orbital (LO) area and they are distinguished by the following characteristics.

Boundaries VO/VLO/LO

In VO, the cells of the layer II are not arranged in a recognizable structure. They are unequally spread with some cells spreading into the layer I seeking contact to the retrobulbar region. Also some clustering is present in the layer II in VO.

In VLO, the cells of the layers II and III are arranged in curvilinear vertical columns. VLO is usually situated at the ventral notch, the indentation seen on the ventral side of the frontal lobe. The main characteristic of the lateral area (LO) is the clustering of cells in its layer II with a sharp transition of that layer to the layer III.

The VLO differs from its posterior part, VLOp, by the following features. In VLO, the layers III, V and VI are separated by open zones of low cell density. In the posterior part of VLO, distinguished as VLOp, however, all layers are more homogeneous.

Lateral PFC subareas

Boundary of the granular (G) or dysgranular insular cortex (DI) with the dorsal agranular insular area 1 (AId1)

In the frontal part of the PFC, the dorsal agranular insular area 1 (AId1) borders the granular cortex (G), but in the caudal part of the PFC AId1 borders the dysgranular cortex (DI).

Columns are seen very clearly in the layers V and VI in AId1, not at all or much less impressive and less closely packed in G or DI.

The cells of layer V are smaller in AId1 than in G or DI.

The layers II, III and IV are homogeneous in DI, but in AId1 the layer IV is absent and the layers II and III are well distinguishable from each other.

The cells of the layer III are less densely packed in AId1 than in G or DI.

Boundary AId1/AId2 (dorsal agranular insular area 2)

Columns are seen in both areas, but they are more densely packed in AId2 than in AId1.

The cells of the layer V are smaller in AId2 than in AId1.

The cells of the layer III are less densely packed in AId2 than in AId1.

The layer II is broad in both areas. In AId1 layer II cells are densely packed, but in AId2 the layer II is broken by clefts, its cells partake in the columnar structure of the area and some cells spread into the layer I.

Boundary AId1/AIp (posterior agranular insular area)

In the posterior agranular insular area (AIp), the cortical layers and the claustrum are well separated from each other. If the cell-sparse zones between the layers are included as sublayers, 8 or more (sub)layers can be distinguished. In AId1, the layers are contingent and a columnar arrangement of the cells of the layers V and VI is visible. The cells of layer V of AIp are smaller than the cells of layer V in AId1.

Boundary AId2/LO

Columns are seen in the layers VI, V and II in AId2, but not in LO. Layer I is narrow in LO, broad in AId2. The layer II in AId2 is broad and cells spread to layer I. In LO the layer II shows marked clustering of cells.

Appendix 2

Abbreviations in the Franklin and Paxinos atlas (2008)

AI:

Agranular insular cortex

AID:

Agranular insular cortex, dorsal part

AIP:

Agranular insular cortex, posterior part

AIV:

Agranular insular cortex, ventral part

Cg1:

Cingulate cortex, area 1

Cg2:

Cingulate cortex, area 2

Cl:

Claustrum

DI:

Dysgranular insular cortex

DLO:

Dorsolateral orbital cortyex

DP:

Dorsal peduncular cortex

fmi:

Forceps minor of the corpus callosum

Fr3:

Frontal cortex, area3

FrA:

Frontal association cortex

GI:

Granular insular cortex

IL:

Infralimbic cortex

LO:

Lateral orbital cortex

M2:

Secondary motor cortex

MO:

Medial orbital cortex

PrL:

Prelimbic cortex

RSD:

Retrosplenial dysgranular cortex

RSG:

Retrosplenial granular cortex

VO:

Ventral orbital cortex

Abbreviations in the Hof et al. atlas

ACd:

Anterior cingulate cortex, dorsal part

ACv:

Anterior cingulate cortex, ventral part

AId:

Agranular insular cortex, dorsal part

AIp:

Agranular insular cortex, posterior part

AIv:

Agranular insular cortex, ventral part

CLA:

Claustrum

DP:

Dorsal peduncular area

fa:

Corpus callosum, anterior forceps

FRA:

Frontal association area

FRP:

Frontal pole

GU:

Gustatory cortex

IG:

Indusium griseum

IL:

Infralimbic area

MOs:

Secondary motor cortex

ORBl:

Orbital cortex, lateral part

ORBm:

Orbital cortex, medial part

ORBvl:

Orbital cortex, ventrolateral part

PL:

Prelimbic area

rf:

Rhinal fissure

TTd:

Tenia tecta, dorsal part

Abbreviations in the Rose atlas

ai 1:

Area insularis agranularis anterior

ai 2:

Area insularis agranularis posterior

i 1:

Area insularis granularis anterior

i 2:

Area insularis granularis posterior

IRa α:

Area infraradiata ventralis anterior

IRb α:

Area infraradiata intermedia anterior

IRc α:

Area infraradiata dorsalis anterior

IRa β:

Area infraradiata ventralis posterior

IRb β:

Area infraradiata intermedia posterior

IRc β:

Area infraradiata dorsalis posterior

Praecag:

Regio praecentralis agranularis

Praecgr:

Regio praecentralis granularis

Abbreviations in the Wree et al. study

C1; 2; 3; 4:

Area cingularis 1; 2; 3; 4

Cl:

Claustrocortex

Prc_m :

Area praecentralis medialis