We conclude that selective accumulation of ptau in the anterodorsal thalamic nucleus disrupts head direction signaling, leading a change in orienting behaviour during initial spatial learning.

Dysfunction of thalamic head direction cells may be a 'preclinical' cognitive biomarker of dementia

We expressed mutant human tau in the anterodorsal nucleus of the mouse thalamus, which contains a high density of head direction cells.

These mice exhibited spatial disorientation during initial spatial learning, which could be explained by lower directionality of cells recorded in this nucleus

Spatial disorientation is an early sign of dementia. What neural circuit mechanism explains this?

We previously found that the human anterodorsal nucleus of the thalamus is highly vulnerable to pathological tau (ptau), even before ptau spreads across the cortex.

link.springer.com/article/10.1...

Thanks Abhilasha! And still using the same amplifiers. ADn HD cells also have a distinctive sound that is different from neurons in AV, DG, LD, etc.

We suggest this ‘HD hub’ consists of different cell types and circuits, acting as ‘parallel channels’ coordinating sensory-modulated updates of the head direction for spatial navigation.

11/11

Type III HD cells were highly unusual as they avoided the TRN and projected ventrally to the cortex. These cells had distinctive twisted dendrites, were CR+, and were located in the dorsomedial ADn.

10/11

We found 3 types of projection patterns: type I HD cells formed collaterals in the thalamic reticular nucleus (TRN) and cortex, projecting via the striatum and cingulum bundle. Type II HD cells additionally innervated the dorsomedial striatum.

9/11

We found a mediolateral gradient of calretinin (CR)-expressing HD cells, with CR+ cells tending to have narrower HD tuning widths, lower firing rates, and produced fewer spikes during rebound bursts compared to CR- cells.

8/11

We confirmed that HD cells could respond to sound stimuli, but found that not all cells were responsive, suggesting cell-type-specificity. Also, some sound-responsive cells were ‘boosted’ by muscle twitches. Other HD cells strongly increased or decreased firing during running periods.

7/11

We recorded HD cells with a range of short-latency responses to light pulses e.g. ‘ON inhibition OFF excitation’, or ‘ON excitation’. We suggest these patterns could help anchor various allocentric cues.

6/11

We used single neuron extracellular recordings and juxtacellular labelling to define the firing patterns, neurochemical profiles, and connectivity of individual HD cells in the ADn of awake mice.

5/11

Interestingly, some but not all HD cells stop firing when the animal is held by the experimenter (Taube, J Neurosci 1995) and others increase firing in response to sensory stimuli (Blanco-Hernandez et al, Nat Neuro 2024). This hints at some diversity of thalamic HD cells.

4/11

A high density of HD cells are found in the anterodorsal nucleus of the thalamus (ADn). The central dogma is that they act as a single functional unit for routing HD signals to the cortex.

3/11