Laminar and temporal heterogeneity of NMDA/metabotropic glutamate receptor binding in posterior cingulate cortex.

Both N-methyl-D-aspartate (NMDA) and quisqualate/AMPA-insensitive metabotropic glutamate (mGlu) receptors mediate plasticity induction in neocortex, but their interlaminar distribution in cortical microcircuits is largely unknown. We used (+)(3)H-MK801 and (3)H-glutamate binding plus saturating concentrations of NMDA, AMPA, and quisqualate to autoradiographically map NMDA and mGlu receptor sites by lamina in posterior cingulate cortex in adult male rats. Specific binding at NMDA receptor sites in laminae II/III and VI was significantly reduced in comparison to other laminae. Brains prepared from rats killed during dark phase of a 12h/12h light/dark cycle showed a mean 129% increase in overall (+)(3)H-MK801 binding versus light phase brains but retained reduced binding densities in laminae II/III and VI. In contrast to NMDA findings, specific binding at mGlu sites was consistently elevated during light phase in both laminae II/III and VI. Specific (3)H-glutamate binding in dark-phase brains showed an overall 147% increase versus light phase binding but did not retain significant interlaminar heterogeneity. Interpreted in accordance with our physiologically derived models of hippocampo-cortical microcircuitry, these results suggest that spatial and temporal variations in glutamate receptor distribution may play an important role in intracingulate neural processing of afferent input from hippocampus.

Long-term plasticity in cingulate cortex requires both NMDA and metabotropic glutamate receptor activation.

We tested whether induction of homosynaptic long-term potentiation and long-term depression of synaptic strength in posterior cingulate cortex requires NMDA and/or metabotropic glutamate (mGlu) receptor activation. In in-vitro slices of rat posterior cingulate cortex, the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid (D-AP5; 15-20 microM) blocked induction of both long-term potentiation and long-term depression of mono- and polysynaptic population potentials in deep laminae. In contrast, DL-2-amino-3-phosphonopropionic acid (DL-AP3; 15-25 microM), a selective mGlu receptor antagonist, blocked homosynaptic long-term potentiation and long-term depression of monosynaptic transmission, but was ineffective in blocking the induction of either type of plasticity at polysynaptically-driven sites. The selective mGlu receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), induced a marked depression of subicular-evoked monosynaptic potentials which reversed upon drug washout, but produced little depression of polysynaptic responses. We conclude that metabotropic glutamate receptor activation is necessary for the induction of long-term synaptic plasticity only at monosynaptic subiculo-cingulate terminals, while NMDA receptor activation is necessary for the induction of long-term potentiation/long-term depression of both mono- and polysynaptic pathways.

Long-term potentiation and depression of synaptic transmission in rat posterior cingulate cortex.

We used stimulation of corpus callosum (CAL) and the subiculo-cingulate tract (SCT), in an in vitro brain slice preparation, to study activity-dependent changes in synaptic efficacy in posterior cingulate cortex (PCC). SCT stimulation monosynaptically excites the apical dendrites of deep laminae (V-VI) pyramidal neurons, while CAL afferents drive these same cells via synapses on their basal dendrites. In contrast, most superficial laminae (II/III-IV) pyramids appear to be driven polysynaptically via ascending axonal collaterals of deep pyramids. In slices retaining these connectivities, we contrasted characteristics of synaptic plasticity in superficial vs deep laminae field and intracellular potentials evoked by conditioning stimuli given at frequencies of 100, 20, 8, 5 and 1 Hz. Tetanic stimulation (100 Hz) of SCT or CAL yielded homosynaptic long-term potentiation (LTP) of each pathway, while stimulus trains of 8-20 Hz did not. 1-5 Hz stimulation of SCT and CAL elicited homosynaptic long-term depression (LTD) of synaptic strength in each pathway. Associative LTD was induced by interleaving 5 Hz pulses to the SCT pathway with 100 Hz theta-burst stimulation of CAL, but was not induced when these stimulus loci were switched. Heterosynaptic non-associative LTD was also observed in the alternate pathway following tetanization of either SCT or CAL. In all cases, LTP and LTD were observed only in deep laminae recordings. In contrast, superficial records showed only paired-pulse facilitation and short-term post-tetanic potentiation. In in vivo experiments in anaesthetized rats, PCC responses to SCT stimulation were contrasted with responses to stimulation of anteroventral and anterodorsal thalamic nuclei (AV/AD). SCT-elicited field potentials closely resembled those evoked in the slice, with maximal amplitude tuned to the 4-8 Hz frequency band. AV/AD stimulation elicited field potentials which were not frequency tuned. Overall, these data suggest that the acute circuit properties of PCC superficial laminae, modulated by thalamic input and synaptic plasticity in deep laminae, can transform hippocampal synaptic inflow before relaying it to extracingulate targets.

Microcircuitry of posterior cingulate cortex in vitro: electrophysiology and laminar analysis using the current source density method.

We used current source density (CSD) analysis of a laminar profile of subicular stimulus-evoked field potentials recorded in cortical slices in vitro to characterize the interlaminar microcircuitry of posterior cingulate cortex. Neuroanatomic and electrophysiologic data indicate that subiculocingulate tract (SCT) afferents monosynaptically excite apical dendrites of deep laminae (V-VI) neurons, evoking pure EPSPs, while superficial laminae (II/III-IV) neurons are driven polysynaptically, evoking a mixture of longer latency EPSPs and IPSPs. Consistent with this model, CSD analysis of field potential laminar profiles supports the conclusion that activation of excitatory subicular afferent terminal fields in superficial laminae of cingulate cortex elicits primary monosynaptic activation of apical dendrites of deep lamina (V-VI) pyramids. Subsequent EPSP propagation to the somata of these pyramids generated synchronous action potential discharges which appeared to elicit delayed polysynaptic activation of superficial laminae pyramids and interneurons. Latency differences between SCT-stimulus-evoked EPSPs and action potentials in superficial and deep laminae were minimized by stimulus train frequencies of 5-8 Hz, indicating that the proposed microcircuitry can show functional tuning at frequencies characteristic of hippocampal neuronal activity (theta). Such tuning suggests that hippocampal output activity frequency and phase locked to theta rhythm will be preferentially gated through cingulate cortex.

Autoradiographic localization of muscimol and baclofen binding sites in rodent cingulate cortex.

The laminar distribution of 3H-muscimol and 3H-baclofen binding was analyzed autoradiographically in areas 29c and 24b of rat cingulate cortex. Muscimol binding was heterogeneous in area 29c with a single peak in layer Ia of 320 +/- 26 grains per 2500 micron2. Binding in deeper layers was between 46% and 71% of that in layer Ia. There was a marked diurnal variation in muscimol binding in area 29c such that binding was elevated by 320% in layer Ia of brains perfused at 22:00-01:00 versus those perfused at 11:00-14:00. Muscimol binding in area 24b was uniform across all layers and was higher than that in area 29c except for in layer Ia. Baclofen binding was homogeneous in both areas, but was 120% greater in area 24b than in area 29c, and showed no diurnal variations. To localize muscimol binding sites at the cellular level, two types of lesion experiments were conducted in area 29c. First, ablation of neurons intrinsic to this cortex with the neurotoxin ibotenic acid reduced muscimol binding to homogeneity with a 70% reduction in layer Ia and a 29-42% reduction in deeper layers. Second, knife cuts, which were placed to isolate cingulate cortex from fiber pathways originating extrinsically, increased muscimol binding in all layers except layer Ia. Conversely, knife cuts which isolated superficial from deep layers yielded a marked drop in muscimol binding in all layers. In conclusion, muscimol binding sites are heterogeneously distributed in area 29c with peak binding in layer Ia at night.(ABSTRACT TRUNCATED AT 250 WORDS)