Sang-Yoon Kim, Woochang Lim – Recent Articles

arXiv:2310.11635v2 Announce Type: replace Abstract: The basal ganglia (BG) in the brain exhibit diverse functions for motor, cognition, and emotion. Such BG functions could be made via competitive harmony between the two competing pathways, direct pathway (DP) (facilitating movement) and indirect pathway (IP) (suppressing movement). As a result of break-up of harmony between DP and IP, there appear pathological states with disorder for movement, cognition, and psychiatry. In this paper, we are concerned about the Huntington's disease (HD), which is a genetic neurodegenerative disorder causing involuntary movement and severe cognitive and psychiatric symptoms. For the HD, the number of D2 SPNs ($N_{\rm D2}$) is decreased due to degenerative loss, and hence, by decreasing $x_{\rm D2}$ (fraction of $N_{\rm D2}$), we investigate break-up of harmony between DP and IP in terms of their competition degree ${\cal C}_d$, given by the ratio of strength of DP (${\cal S}_{DP}$) to strength of IP (${\cal S}_{IP}$) (i.e., ${\cal C}_d = {\cal S}_{DP} / {\cal S}_{IP}$). In the case of HD, the IP is under-active, in contrast to the case of Parkinson's disease with over-active IP, which results in increase in ${\cal C}_d$ (from the normal value). Thus, hyperkinetic dyskinesia such as chorea (involuntary jerky movement) occurs. We also investigate treatment of HD, based on optogenetics and GP ablation, by increasing strength of IP, resulting in recovery of harmony between DP and IP. Finally, we study effect of loss of healthy synapses of all the BG cells on HD. Due to loss of healthy synapses, disharmony between DP and IP increases, leading to worsen symptoms of the HD.

We consider a biological network of the hippocampal dentate gyrus (DG). The DG is a pre-processor for pattern separation which facilitates pattern storage and retrieval in the CA3 area of the hippocampus. The main encoding cells in the DG are the granule cells (GCs) which receive the input from the entorhinal cortex (EC) and send their output to the CA3. The activation degree of GCs is so low (~ 5%). This sparsity has been thought to enhance the pattern separation. We investigate the dynamical origin for winner-take-all (WTA) competition which leads to sparse activation of the GCs. The whole GCs are grouped into lamellar clusters. In each GC cluster, there is one inhibitory (I) basket cell (BC) along with excitatory (E) GCs. There are three kinds of external inputs into the GCs; the direct excitatory EC input, the indirect inhibitory EC input, mediated by the HIPP (hilar perforant path-associated) cells, and the excitatory input from the hilar mossy cells (MCs). The firing activities of the GCs are determined via competition between the external E and I inputs. The E-I conductance ratio ${\cal{R}}_{\rm E-I}^{\rm (con)*}$ (given by the time average of the external E to I conductances) may represents well the degree of such external E-I input competition. GCs become active when their $\cal{R}_{\rm E-I}^{\rm (con)*}$ is larger than a threshold ${\cal{R}}_{th}^*$, and then the mean firing rates of the active GCs are strongly correlated with $\cal{R}_{\rm E-I}^{\rm (con)*}$. In each GC cluster, the feedback inhibition of the BC may select the winner GCs. GCs with larger $\cal{R}_{\rm E-I}^{\rm (con)*}$ than the threshold ${\cal{R}}_{th}^*$ survive, and they become winners; all the other GCs with smaller $\cal{R}_{\rm E-I}^{\rm (con)*}$ become silent. The WTA competition occurs via competition between the firing activity of the GCs and the feedback inhibition from the BC in each GC cluster.

Author: Sang-Yoon Kim, Woochang Lim

Break-up and Recovery of Harmony between Direct and Indirect Pathways in The Basal Ganglia; Huntington’s Disease and Treatment

Dynamical Origin for Winner-Take-All Competition in A Biological Network of The Hippocampal Dentate Gyrus. (arXiv:2105.06057v1 [q-bio.NC])