The subiculum: what it does, what it might do, and what neuroanatomy has yet to tell us

Abstract

The subiculum is a pivotal but under-investigated structure positioned between the hippocampus proper and entorhinal and other cortices, as well as a range of subcortical structures. The subiculum has a range of electrophysiological and functional properties which are quite distinct from its input areas; given the widespread set of cortical and subcortical areas with which it interacts, it is able to influence activity in quite disparate brain regions. The rules governing plasticity of synaptic transmission in the hippocampal-subicular axis are poorly understood; this axis appears to share some properties in common with the hippocampus proper, but behaves quite differently in other respects. Equally, its functional properties are not well understood; it plays an important but ill-defined role in spatial navigation, mnemonic processing and control of the response to stress. Here, I review investigations of synaptic plasticity in the hippocampal-subicular pathway, recordings of subicular neurons in the freely moving behaving animal, the effects of behavioural and other stressors on subicular synaptic plasticity, and anatomical data on the dorso-ventral organization of the subiculum in relation to the hypothalamic-pituitary-adrenal (HPA) axis. I argue that there is a dorso-ventral segregation of function within the subiculum: the dorsal component appears principally concerned with the processing of information about space, movement and memory, whereas the ventral component appears to play a major regulatory role in the inhibition of the HPA axis.

Fig. 1

The hippocampal formation (A) and location of subiculum (B), indicated as ‘s’ in a section through the hippocampal formation. [From: Fuster, J.M.Memory in the Cerebral Cortex: An Empirical Approach to Neural Networks in the Human and Nonhuman Primate.Cambridge, MA:The MIT Press,1995,p. 26.Copyright MIT Press.]

Fig. 2

Intrinsic connections of the hippocampal formation, including the recently discovered projection from perirhinal cortex to CA1 and subiculum.

Fig. 3

(A) Neurons in proximal CA1 project to distal subiculum, neurons in mid-CA1 project to mid-subiculum and neurons in distal CA1 project across the CA1–subiculum border into proximal subiculum. (B) Depth profile of subicular fEPSPs following stimulation in area CA1. (i) and (ii) indicate the positions of stimulating and recording electrodes located in area CA1 and subiculum, respectively; (iii) is a plot of fEPSPs following stimulation in successive locations as the stimulating electrode is moved towards area CA1 of the hippocampus. (C) Schematic drawings of the coronal sections indicating the positions of stimulating and recording electrodes located in dorsal subiculum and CA1, respectively (3.3 and 4.8 mm behind bregma; adapted from Paxinos & Watson, 1997). Also shown are the corresponding field potentials recorded after dorsal subiculum stimulation at the two sites in CA1.

Fig. 4

(A) Effects of high-frequency stimulation (HFS) on the amplitude of fEPSPs; post-HFS fEPSP values are expressed as a percentage of the pre-HFS baseline. The insets are representative EPSPs pre- and post-LTP induction. The letters above the averaged data represent the time point from which the inset traces are taken. (B) Paired-pulse facilitation in the CA1–subiculum pathway for the intervals indicated. Bars represent mean peak amplitude for fEPSP1 (black) and fEPSP2 (hatched) (**P < 0.01, *P < 0.05). Data are normalized to fEPSP1 (100%). (C) Changes in PPF after LTP induction. Mean PPF before (black) and after (hatched) HFS that induced LTP (**P < 0.01, *P < 0.05).

Fig. 5

Effects of LFS (10 Hz) on the amplitude of fEPSPs. The post-LFS values are expressed as a percentage of the prestimulation baseline ( ± SEM). (ii) A bar chart showing percentage PPF both pre- and post-LFS for 50 and 100 ms ISIs. Note the increase in facilitation at both ISIs post-LFS. (iii) Effects of stress and LFS (10 Hz) on the amplitude of fEPSPs. The post-LFS values are expressed as a percentage of the prestimulation baseline ( ± SEM). (iv) A bar chart showing percentage PPF both pre- and post-LFS for the 50 and 100 ms ISIs. Note the decrease in facilitation at 50 ms ISI post-LFS and PPD at the 100 ms ISI. (B) Effects of LPS (closed circle) and saline (open circle) on synaptic transmission over a 6-h period. No significant differences were noted between the two groups. (C). LPS (closed circle) blocks LTP induction compared with saline-injected (open circle) animals.

Fig. 6

Examples of normalized autocorrelation histograms (ACHs) for three bursting units (A–C), a regular spiking unit (D), a theta-modulated unit (E) and a fast-spiking unit (F). ACHs were normalized by dividing the number of intervals in each 1-ms bin by the total session time (s); this reveals the rate (Hz) of each interval. The corresponding overlaid spike waveforms (grey) and mean waveform (black) are shown to the right of each ACH.

Fig. 7

From C. A. Lowry (fig. 3). Functional subsets of serotonergic neurones: implications for control of the hypothalamic-pituitary-adrenal axis. Journal of Neuroendocrinology, 2002, 14, 911–923. Copyright Blackwell Publishing. ¹Projections from the anterior cingulate to the dorsal hypothalamic area and lateral periaqueductal grey. ²Projections from the infralimbic and prelimbic cortices to the anterior hypothalamic nucleus, ventromedial hypothalamus and dorsolateral periaqueductal grey. ac, anterior commissure; AHNp, anterior hypothalamic nucleus, posterior part; AI, agranular insular cortex; AON, anterior olfactory nucleus; AP, anterior pituitary; B8, B8 serotonergic cell group, median raphe nucleus, interfascicular dorsal raphe nucleus; BSTMA, bed nucleus of the stria terminalis, medial division, anterior part; BSTMPI, bed nucleus of the stria terminalis, medial division, posterointermediate part; BSTMV, bed nucleus of the stria terminalis, medial division, ventral part; CA1, field CA1 of hippocampus; cc, corpus callosum; Cg1, cingulate cortex, area 1; CL, claustrum; DA, dorsal hypothalamic area; DEn, dorsal endopiriform nucleus; DLPAG, dorsolateral periaqueductal grey; DMNvl, dorsomedial hypothalamic nucleus, ventrolateral part; Ent, entorhinal cortex; IML, intermediolateral cell column; IL, infralimbic cortex; LHb, lateral habenular nucleus; LPAG, lateral periaqueductal grey; LSv, lateral septal nucleus, ventral part; MeAD, medial amygdaloid nucleus, anterodorsal part; MeApv, medial amygdaloid nucleus, posteroventral part; MM, medial mammillary nucleus, medial part; MPA, medial preoptic area; ox, optic chiasm; PaDC, paraventricular hypothalamic nucleus, dorsal cap; PeF, perifornical nucleus; PH, posterior hypothalamic area; Pir, piriform cortex; PMD, premammillary nucleus, dorsal part; PMV, premammillary nucleus, ventral part; PRh, perirhinal cortex; PrL, prelimbic cortex; PV, paraventricular thalamic nucleus; RCh, retrochiasmatic area; Re, reunions thalamic nucleus; ROb, raphe obscurus; RPa, raphe pallidus; S, subiculum; SChsh, suprachiasmatic nucleus, shell region; SPa, subparaventricular zone of the hypothalamus; SuMm, supramammillary nucleus, medial part; TM, tuberomammillary nucleus; VMH, ventromedial hypothalamic nucleus.

Fig. 8

A model of subicular function(s) (see text for full details). Here, synaptic transmission and anatomical connectivity run from left to right (a deliberate simplification); information of differing types (mnemonic etc.) derives from various anteceding cortical and subcortical circuits, and is projected to the subiculum, converging in particular patterns, thereby giving rise to differing neuronal response types. EC, entorhinal cortex; Hypo, hypothalamus; PRC, perirhinal cortex; PFC, prefrontal cortex; PC, parietal cortex. For simplification no details of distal–proximal distribution of fibres is provided (but these do vary).