Modular microcircuit organization of the presubicular head-direction map

Balsamo, Giuseppe; Blanco-Hernández, Eduardo; Liang, Feng; Naumann, Robert K.; Coletta, Stefano; Burgalossi, Andrea; Preston-Ferrer, Patricia

doi:10.1016/j.celrep.2022.110684

Cited by 8 publications

(6 citation statements)

References 128 publications

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“…This suggests the possibility of anatomically mapping the input and output of the circuitry specializing in head direction computations 30 . Our reported topography of presubicular projections classes is consistent with the recently observed local modularity of the head-direction microcircuit 31 , and may help clarify the relationship between the egocentric and allocentric spatial and episodic representations of the cortico-hippocampal system 32 .…”

Section: Discussionsupporting

confidence: 89%

Unsupervised classification of brain-wide axons reveals neuronal projection blueprint

Wheeler,

Banduri,

Sankararaman

et al. 2023

Preprint

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Long-range axonal projections are quintessential determinants of network connectivity, linking cellular organization and circuit architecture. Here we introduce a quantitative strategy to identify, from a given source region, all “projection neuron types” with statistically different patterns of anatomical targeting. We first validate the proposed technique with well-characterized data from layer 6 of the mouse primary motor cortex. The results yield two clusters, consistent with previously discovered cortico-thalamic and intra-telencephalic neuron classes. We next analyze neurons from the presubiculum, a less-explored region. Extending sparse knowledge from earlier retrograde tracing studies, we identify five classes of presubicular projecting neurons, revealing unique patterns of divergence, convergence, and specificity. We thus report several findings: (1) individual classes target multiple subregions along defined functions, such as spatial representation vs. sensory integration and visual vs. auditory input; (2) all hypothalamic regions are exclusively targeted by the same class also invading midbrain, a sharp subset of thalamic nuclei, and agranular retrosplenial cortex; (3) Cornu Ammonis, in contrast, receives input from the same presubicular axons projecting to granular retrosplenial cortex, also the purview of a single class; (4) path distances from the presubiculum to the same targets differ significantly between classes, as do the path distances to distinct targets within most classes, suggesting fine temporal coordination in activating distant areas; (5) the identified classes have highly non-uniform abundances, with substantially more neurons projecting to midbrain and hypothalamus than to medial and lateral entorhinal cortex; (6) lastly, presubicular soma locations are segregated among classes, indicating topographic organization of projections. This study thus demonstrates that classifying neurons based on statistically distinct axonal projection patterns sheds light on the functional organizational of their circuit.

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Section: Discussionsupporting

confidence: 89%

Unsupervised classification of brain-wide axons reveals neuronal projection blueprint

Wheeler,

Banduri,

Sankararaman

et al. 2023

Preprint

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show abstract

“…Cluster analysis (Fig. 2D) provided no evidence for subpopulations of layer 3 cells (but see Balsamo et al, 2022). We tested the hypothesis by independent activation of ATN and RSC afferents using photostimulation at two different light frequencies.…”

Section: Resultsmentioning

confidence: 95%

“…Are single layer 3 pyramidal cells innervated by both ATN and RSC afferents? It seemed likely since the probability of connection to a given cell was 84% for ATN fibers and 85% for RSC afferents, and cluster analysis (Figure 2D) provided no evidence for subpopulations of layer 3 cells (but see Balsamo et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

“…1K and cf. Balsamo et al 2022). The anatomical fine structure revealed microzones containing a high density of ATN-positive fibers, but not RSC fibers, in upper layer 3.…”

Section: Discussionmentioning

confidence: 99%

“…Head direction cells are found in the superficial and deep layers of dorsal presubiculum, also termed postsubiculum (Boccara et al, 2010), and most layer 3 neurons in the dorsal presubiculum are head direction cells (Tukker et al, 2015; Preston-Ferrer et al, 2016). These cells receive monosynaptic head direction inputs from the anterior thalamus (Nassar et al, 2018; Peyrache et al, 2015; Balsamo et al, 2022). Lesions of the PrS impair the visual landmark control of a cell’s preferred direction in ATN and in LMN (Goodridge and Taube, 1997; Yoder et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Projection-specific integration of convergent thalamic and retrosplenial signals in the presubicular head direction cortex

Richevaux

Lim

Nassar

et al. 2023

Preprint

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Head-direction (HD) signals function as the brain's internal compass. They are organized as an attractor, and anchor to the environment via visual landmarks. This association might happen in the dorsal presubiculum. We find converging monosynaptic excitatory connections from anterior thalamic nucleus and from retrosplenial cortex on single layer 3 presubicular neurons. Independent dual wavelength photostimulation of these inputs in slices leads to action potential generation preferentially for near-coincident inputs, sending an integrated HD signal to medial entorhinal cortex. Layer 4 neurons send their axons to the lateral mammillary nucleus. However, their dendrites avoid overlap with thalamic and retrosplenial axons. Action potentials in layer 4 neurons may be initiated following di-synaptic excitation via layer 3, indicating that landmark updating of HD signals in the lateral mammillary nucleus is a two-step process. Thus, a coherent sense of orientation involves projection specific translaminar processing in the presubiculum.

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Plasticity of neuronal dynamics in the lateral habenula for cue-punishment associative learning

Congiu,

Mondoloni,

Zouridis

et al. 2023

Mol Psychiatry

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The brain’s ability to associate threats with external stimuli is vital to execute essential behaviours including avoidance. Disruption of this process contributes instead to the emergence of pathological traits which are common in addiction and depression. However, the mechanisms and neural dynamics at the single-cell resolution underlying the encoding of associative learning remain elusive. Here, employing a Pavlovian discrimination task in mice we investigate how neuronal populations in the lateral habenula (LHb), a subcortical nucleus whose excitation underlies negative affect, encode the association between conditioned stimuli and a punishment (unconditioned stimulus). Large population single-unit recordings in the LHb reveal both excitatory and inhibitory responses to aversive stimuli. Additionally, local optical inhibition prevents the formation of cue discrimination during associative learning, demonstrating a critical role of LHb activity in this process. Accordingly, longitudinal in vivo two-photon imaging tracking LHb calcium neuronal dynamics during conditioning reveals an upward or downward shift of individual neurons’ CS-evoked responses. While recordings in acute slices indicate strengthening of synaptic excitation after conditioning, support vector machine algorithms suggest that postsynaptic dynamics to punishment-predictive cues represent behavioral cue discrimination. To examine the presynaptic signaling in LHb participating in learning we monitored neurotransmitter dynamics with genetically-encoded indicators in behaving mice. While glutamate, GABA, and serotonin release in LHb remain stable across associative learning, we observe enhanced acetylcholine signaling developing throughout conditioning. In summary, converging presynaptic and postsynaptic mechanisms in the LHb underlie the transformation of neutral cues in valued signals supporting cue discrimination during learning.

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Modular microcircuit organization of the presubicular head-direction map

Cited by 8 publications

References 128 publications

Unsupervised classification of brain-wide axons reveals neuronal projection blueprint

Unsupervised classification of brain-wide axons reveals neuronal projection blueprint

Projection-specific integration of convergent thalamic and retrosplenial signals in the presubicular head direction cortex

Plasticity of neuronal dynamics in the lateral habenula for cue-punishment associative learning

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