The anterior thalamus provides a subcortical circuit supporting memory and spatial navigation

Abstract

The anterior thalamic nuclei (ATN), a central component of Papez' circuit, are generally assumed to be key constituents of the neural circuits responsible for certain categories of learning and memory. Supporting evidence for this contention is that damage to either of two brain regions, the medial temporal lobe and the medial diencephalon, is most consistently associated with anterograde amnesia. Within these respective regions, the hippocampal formation and the ATN (anteromedial, anteroventral, and anterodorsal) are the particular structures of interest. The extensive direct and indirect hippocampal-anterior thalamic interconnections and the presence of theta-modulated cells in both sites further support the hypothesis that these structures constitute a neuronal network crucial for memory and cognition. The major tool in understanding how the brain processes information is the analysis of neuronal output at each hierarchical level along the pathway of signal propagation coupled with neuroanatomical studies. Here, we discuss the electrophysiological properties of cells in the ATN with an emphasis on their role in spatial navigation. In addition, we describe neuroanatomical and functional relationships between the ATN and hippocampal formation.

Keywords: anterior thalamus; head direction cells; memory; spatial navigation; theta rhythm.

Figure 1

The localization of the ATN in the rat brain. Top: coronal and sagittal sections of rat brain are shown (Paxinos and Watson, 1998) with the ATN indicated in green, red and blue and whole area of the thalamus in gray. The dashed black lines depict the spatial relation between presented sections. The dashed red rectangles denote the extent of coronal and sagittal sections, respectively, presented below. Abbreviations: 3V, 3rd ventricle; AD, anterodorsal thalamic nucleus; AV, anteroventral thalamic nucleus; AM, anteromedial thalamic nucleus; AMV, anteromedial thalamic nucleus, ventral part; CL, centrolateral thalamic nucleus; IAM, interanteromedial thalamic nucleus; ic, internal capsule; LD, laterodorsal thalamic nucleus; LP, lateral posterior thalamic nucleus; MD, mediodorsal thalamic nucleus; mt, mammillothalamic tract; PC, paracentral thalamic nucleus; PF, parafascicular thalamic nucleus; PT, paratenial thalamic nucleus; PVA, paraventricular thalamic nucleus, anterior part; RE, reuniens thalamic nucleus; RT, reticular thalamic nucleus; sm, stria medullaris of the thalamus; st, stria terminalis; VA, ventral anterior thalamic nucleus; VL, ventrolateral thalamic nucleus; VM, ventromedial thalamic nucleus.

Figure 2

The color-coded diagram presents the main direct connections of the anterodorsal (AD), anteroventral (AV), and anteromedial (AM) thalamic nuclei in the rat brain. Black arrows depict reciprocal connections, green efferents, and red afferents of the three anterior thalamic nuclei (ATN). Structures in blue contain head direction cells, and so constitute a part of the hierarchically organized head direction system (Clark and Taube, 2012). The various indirect connections of the ATN, along with the connections between other highlighted structures, are not included in this scheme.

Figure 3

The “extended-hippocampal system” proposed by Aggleton et al. (2010). Color-coded diagram depicts how, in the rat, the hippocampal formation is associated with three sets of parallel mammillary body—anterior thalamic connections. Connectivity studies in the monkey brain (macaque) support the same overall scheme for primates (e.g., Vann et al., 2007). The connections solely conveyed in the fornix are shown as dashed lines. Double-headed arrows depict reciprocal connections. Abbreviations: DtG, dorsal tegmental nucleus of Gudden; MTT, mammillothalamic tract; VtGp, ventral tegmental nucleus of Gudden, pars posterior. (Note, the lateral dorsal thalamic nucleus has not been included above as, unlike the anterior thalamic nuclei, it receives few, if any, mammillary body inputs. The interoanteromedial nucleus has not been included given its uncertain status in the primate brain).

Figure 4

Head direction-by-theta cells recorded in anteroventral thalamic nucleus (Tsanov et al., 2011a). (A) Anatomical location of chronically implanted tetrodes aimed at anteroventral nucleus (bundle of eight tetrodes). On the left, the histological slide showing the location of chronically implanted tetrodes marked with the black arrow. Area of anteroventral nucleus is indicated with white dashed line and anterodorsal nucleus with green dashed line. On the right, location of anteroventral and anterodorsal nuclei is shown on the modified section from the rat brain atlas (Paxinos and Watson, 1998). The dashed blue rectangle denotes the extent of the histological section on left. (B) On the left, the path of the animal (black line) with superimposed firing activity of head direction-by-theta unit (blue dots) recorded during 16-min session in a square arena (64 × 64 × 25 cm). On the right, the polar plot represents the distribution of time heading in different directions across all time bins of the trial (yellow) and the distribution of head directions for time bins when a spike was recorded from the cell (black). (C) The same signal can be plotted as firing rate vs. head direction tuning plot for head direction-by-theta units. (D,E) The spike waveform (D) and the autocorrelogram of spiking activity calculated for 10/10 ms (E) for four anteroventral head direction-by-theta units, respectively. For the spike waveform, the solid curve represents the mean, and the dashed curve represents the SD. The clear isolation of the neuronal extracellular response was identified by the absence of correlations within the first 2 ms of the refractory period. (F) The 1000 ms autocorrelograms of four head direction-by-theta units. The fitted vertical red line indicates the relative amplitude of the sinusoid component of the autocorrelogram, visualizing the degree of autocorrelogram rhythmicity.

Figure 5

Theta modulated cells from the anteromedial thalamic nucleus. (A) Recording sites and three examples of theta modulated cells recorded in the superficial part of anteromedial nucleus. On the left, the histological slide showing the location of chronically implanted tetrodes marked with the black arrow. In this case, three theta modulated cells were recorded in the superficial part of anteromedial nucleus. Estimated location of recorded cells is marked below by green dots on the section from rat brain atlas (Paxinos and Watson, 2006). On the right, parameters of three theta modulated cells recorded in this rat are presented. From the top for each cell, the waveform, autocorrelation for 10 ms, autocorrelation for 1000 ms and interspike interval histogram (ISIH) are presented. All three cells exhibit different firing rate and waveforms, but all are modulated in the theta rhythm frequency, which is visible as 6–10 peaks on 1000 ms autocorrelogram. The ISIH indicates that recorded cells were not bursting neurons (there is no peak of firing before 5 ms). (B) Recording site and example of theta modulated cell recorded in the bottom part of anteromedial nucleus. In the top, the histological slide shows the location of chronically implanted tetrodes, marked with the black arrow. In this case, a theta modulated cell was recorded in the bottom part of anteromedial nucleus (see also estimated position of the cell on the right). Below, the waveform, autocorrelation for 10 ms, autocorrelation for 1000 ms, and ISIH are presented. The 1000 ms autocorrelogram indicates that this cell was modulated in the frequency of theta rhythm and ISIH clearly shows that this cell is a bursting neuron. Recordings were performed in rats chronically implanted with driveable 32-channel microelectrodes organized in tetrodes. Each recording session lasted 20 min and was performed in freely moving rats foraging for food pellets in a circular arena (96 cm diameter). Abbreviations: AM, anteromedial thalamic nucleus; 3 V, third ventricle; AMV, anteromedial thalamic nucleus, ventral part; f, fornix; mt, mammillothalamic tract; sm, stria medullaris of the thalamus.