Localization And Connectivity Of Rodent Equivalent Of The Primate Posterior Cingulate Cortex(Area 23)

Background : The posterior cingulate gyrus in humans and non-human primates(NHP)consists of the retrosplenial cortex(RS),which includes Brodman’s area 29(A29)and area 30(A30),and the posterior cingulate cortex(PCC),which contains Brodmann’s area 23(A23)and area 31(A31).Both the RS and PCC are important components of the default mode network(DMN)and activation of these structures can be observed by the tasks related to default mode network.The PCC is significantly involved in many neurological and psychiatric disorders,including Alzheimer’s disease,schizophrenia,autism,depression,attention-deficit hyperactivity disorder and so on.In the rodents,there also exists homologous RS over the posterior part of the corpus callosum and it is divided into granular part(RSg;equivalent to A29)and the agranular part(RSag;equivalent to A30).However,the region lateral to A30(RSag)has been treated as a lateral agranular region of the RS(RSag)or part of the medial secondary visual cortex(V2MM or 18b)rather than A23.Therefore,whether a homologous A23 exists in rodent is still a mystery.The DMN activation was found in both the RS(A29 and A30)and the regions lateral to A30 in the rodent studies of default mode networks.Based on this finding and the topological location of A29,A30,A23 in primates,we hypothesize that the rodent equivalent of PCC(mainly A23)probably exists in the region lateral to RSag(A30)in rodents and this lateral region roughly corresponds to the RSagl or V2 MM or 18 b.The anatomical and connectional evidence provided in this study supports this hypothesis.Objective:(1)reveal the location and extent of rodent equivalent of the primate PCC(A23);(2)determine brain-wide afferent and efferent connections of homologous A23 in rats and mice.Method : According to the connectional pattern of the primate PCC,A23 mainly receives its afferent projections from the anteromedial thalamic nucleus(AM),while A29 and A30 receive their afferents mainly from the anterodorsal thalamic nucleus(AD)and anteroventral thalamic nucleus(AV).Based on these findings,we first injected the retrograde tracers(FG)into the posterior part of the rat RSagl(V2MM)and RSag regions to examine the distribution of retrograde labeled neurons in AM,AD and AV.Then the anterograde tracers(BDA)were injected into the AM to determine the existence and distribution of labeled axon terminals in the RSagl(V2MM)and RSag regions.Furthermore,we determined the full anterior-posterior(A-P)and medial-lateral(M-L)extent of the labeled terminals in the homologous PCC(A23～)of the rats and mice with a larger anterograde tracer injection covering whole AM extent.Finally,in order to determine brain-wide neural connections of the rat and mouse A23～,anterograde and retrograde tracers were injected respectively into homologous rat/mouse PCC(A23～)to trace axon terminals and cell bodies,respectively.Result: We found that rodent A23～ but not adjoining retrosplenial and visual areas displays strong reciprocal connections with the AM.Based on this finding,we localized A23～ in the rats and mice and determined its extent.Rodent A23～reciprocally connects with the medial pulvinar and claustrum as well as with the anterior cingulate,granular retrosplenial,medial orbitofrontal,postrhinal,and visual and auditory association cortices.The rodent A23～ also projects to the subcortical effectors such as the dorsal striatum,ventral lateral geniculate nucleus,zona incerta,pretectal nucleus,superior colliculus,periaqueductal gray,and brainstem reticular formation.Conclusion : Based on the topographic relationship between A23 and A30,and conservative AM input to A23 as well as the differential expression patterns of some genes between mouse A30 and Rsagl(corresponding to A23～),this study has first revealed the equivalent region of the primate A23 in rat and mouse brains.Afferent and efferent neural connections of the rodent A23～ are comparable to those of the primate A23,while rodent A23～ has different connections from retrosplenial cortex(A29 and A30).Finally,our findings also suggest that the feature of strong AM innervation of A23 could be used to reliably distinguish A23 from adjoining A30,V2 M and medial Pt A across species.Additionally,our results also indicate that the rodents can be used to model monkey and human A23 in future structural,functional,pathological and neuromodulation studies.