Immunostaining for substance P receptor labels GABAergic cells with distinct termination patterns in the hippocampus

Abstract

A specific antiserum against substance P receptor (SPR) labels nonprincipal neurons in the cerebral cortex of the rat (T. Kaneko et al. [1994], Neuroscience 60:199-211; Y. Nakaya et al. [1994], J. Comp. Neurol. 347:249-274). In the present study, we aimed to identify the types of SPR-immunoreactive neurons in the hippocampus according to their content of neurochemical markers, which label interneuron populations with distinct termination patterns. Markers for perisomatic inhibitory cells, parvalbumin and cholecystokinin (CCK), colocalized with SPR in pyramidallike basket cells in the dentate gyrus and in large multipolar or bitufted cells within all hippocampal subfields respectively. A dense meshwork of SPR-immunoreactive spiny dendrites in the hilus and stratum lucidum of the CA3 region belonged largely to inhibitory cells terminating in the distal dendritic region of granule cells, as indicated by the somatostatin and neuropeptide Y (NPY) content. In addition, SPR and NPY were colocalized in numerous multipolar interneurons with dendrites branching close to the soma. Twenty-five percent of the SPR-immunoreactive cells overlapped with calretinin-positive neurons in all hippocampal subfields, showing that interneurons specialized to contact other gamma-aminobutyric acid-ergic cells may also contain SPR. On the basis of the known termination pattern of the colocalized markers, we conclude that SPR-positive interneurons are functionally heterogeneous and participate in different inhibitory processes: (1) perisomatic inhibition of principal cells (CCK-containing cells, and parvalbumin-positive cells in the dentate gyrus), (2) feedback dendritic inhibition in the entorhinal termination zone (somatostatin and NPY-containing cells), and (3) innervation of other interneurons (calretinin-containing cells).

Oxytocin receptor agonists enhance inhibitory synaptic transmission in the rat hippocampus by activating interneurons in stratum pyramidale

“…Morphological studies indicate that the hippocampal formation is richly innervated by axons containing SP (Borhegyi & Leranth, 1997). In addition, GABAergic neurons distributed in all hippocampal sub®elds possess SP receptors (Nakaya et al, 1994;Acsady et al, 1997). In an early work carried out in our laboratory, we found that SP and other peptides of the tachykinin family can powerfully excite rat hippocampal interneurons located in the CA1 region (Dreifuss & Raggenbass, 1986).…”

“…They were deemed to be interneurons if they responded to SP. Indeed, interneurons immunoreactive for SP receptors are distributed in all hippocampal sub®elds, whereas pyramidal cells appear to be devoid of SP receptor immunoreactivity (Nakaya et al, 1994;Acsady et al, 1997). In addition, we previously showed that a majority of nonpyramidal neurons in stratum pyramidale, identi®ed on the basis of their characteristic response to orthodromic activation of Schaffer's collaterals, respond to SP by a reversible, concentrationrelated increase in ®ring (Dreifuss & Raggenbass, 1986).…”

Persistent Pain Produces Stress-like Alterations in Hippocampal Neurogenesis and Gene Expression

“…1 Nonetheless, the complexity of hippocampal cellular architecture and neuronal connectivity may allow fluctuations in gene expression in one subregion to induce cellular and morphologic alterations in neighboring sublayers. However, current findings provide additional evidence that BDNF and NK-1 receptors are involved in pain-or stress-evoked plastic changes in the CNS, particularly within the limbic system.…”

Corresponding decrease in neuronal markers signals progressive parvalbumin neuron loss in MAM schizophrenia model

“…The co-expression of SP receptors and PV has previously been reported for the dentate, CA1, and CA3 subregions of the dorsal HPC (Acsady et al, 1997; Sloviter et al, 2001) and alterations in the co-expression has been used to quantify changes in HPC interneuron number in animal models of epilepsy (Sloviter, 1991; Sloviter et al, 2001; Sloviter et al, 2003), in that substance P receptors are continuously expressed even when activity-dependent PV content is lost. Verifying the extent of PV-expressing interneuron cell survival by measuring the co-expression of SP and PV in the HPC in the MAM model would be consistent with the pathological findings reported in schizophrenia patients.…”