Good Morning

Happy New Year

and Welcome to ANAT0003
 ANAT0003

1300-1400g

2% of total body
weight
SWD 2022
There are ten glia cells for ever neuron

Really! But how do we know this?

 Santiago Ramon Y Cajal 1888

Camillo Golgi 1865

 hTaup301s Knock-in

Somatosensory
Cortex

IV

AT8 Melissa
 Neurons
Principal cells /Interneurons
Golgi Type I and Type II cells
Glial Cells
Astrocytes
Oligodendrocytes
(Schwann Cells)
Tanycytes
Microglia
(Inter Med 49: 331-334, 2010)
 B

D
A B

C
Journal of Anatomy 1959 93 420-433
Gray Type I Gray Type II

Asymmetric Symmetric
Excitatory Inhibitory
NATURE 1959 183 (4675) 1592-1593
 Medium Spiny Neuron

Projects to either the GPext or the

GPint/SNpr

GABA
GAD

Dopamine Receptors of
either D1 or D2 type

Enkephalin
Substance P
Dynorphin

Calbindin
Basal Ganglia
Cerebral
Cortex

Thalamus

Globus
Pallidus

Substantia
Nigra
Striatum
Medium Spiny Cell

Substantia
Nigra
How do we determine patterns of connectivity, and the synaptic
organisation of the brain, and what are the consequences and
the implications of data obtained in these studies?
Glutamate

Dopamine
 M
M
S

Wakoto Matsuda, Takahiro Furuta, Kouichi C. Nakamura, Hiroyuki Hioki, Fumino Fujiyama, Ryohachi Arai, and Takeshi Kaneko. Single Nigrostriatal Dopaminergic Neurons Form Widely Spread and Highly Dense Axonal
Arborizations in the Neostriatum J Neuroscience (2009) 29 (2) 444-453

SWD UCL 2017

Estimation of the number of synapses formed by a single
DA neuron in the striatum in humans

Number of DA neurons in the SNc (one hemisphere) ...............................................382,000

Volume of the striatum (mm3)............................................................................................. 6,280
Volume of striatum per SNc DA neuron (mm3).......................... 0.01644 (6,280/382,000)
Number of synapses formed by one DA neuron in the human striatum.................................
…………………………………………………………………………………………………………………..1,013,068 to 2,430,441
Length of axon per DA neurone…………………………………………………………………………………………4.5 M

SWD UCL 2017

 F

MTT

STN ZI STN
IC
 STN Stimulators OFF

STN Stimulators ON

Thank you Professor Tippu Aziz Oxford

 GABAergic MSN
Projects to GPINT +SNPR
GABAergic MSN D1 Receptor!
Projects to GPEXT
D2 Receptor!

SWD UCL 2014

SWD UCL 2022

Nature. 2010 Jul 29;466(7306):622-6
“Neural circuits of the basal ganglia are critical for motor planning and action
selection. Two parallel basal ganglia pathways have been described, and have been
proposed to exert opposing influences on motor function. According to this classical
model, activation of the ‘direct’ pathway facilitates movement and activation of the
‘indirect’ pathway inhibits movement. However, more recent anatomical and functional
evidence has called into question the validity of this hypothesis. Because this model
has never been empirically tested, the specific function of these circuits in behaving
animals remains unknown. Here we report direct activation of basal ganglia circuitry in
vivo, using optogenetic control of direct- and indirect-pathway medium spiny
projection neurons (MSNs), achieved through Cre-dependent viral expression of
channelrhodopsin-2 in the striatum of bacterial artificial chromosome transgenic mice
expressing Cre recombinase under control of regulatory elements for the dopamine D1
or D2 receptor. Bilateral excitation of indirect-pathway MSNs elicited a parkinsonian
state, distinguished by increased freezing, bradykinesia and decreased locomotor
initiations. In contrast, activation of direct-pathway MSNs reduced freezing and
increased locomotion. In a mouse model of Parkinson’s disease, direct-pathway
activation completely rescued deficits in freezing, bradykinesia and locomotor
initiation. Taken together, our findings establish a critical role for basal ganglia
circuitry in the bidirectional regulation of motor behaviour and indicate that
modulation of direct-pathway circuitry may represent an effective therapeutic
strategy for ameliorating parkinsonian motor deficits.”
SWD UCL 2022
 Nature. 2010 Jul 29;466(7306):622-6

Direct Indirect

Striatum Striatum

GPe

GPi SNPR

Direct 6OH-DA Indirect

Brain Struct Funct. 2016 Mar;221(2):753-814.

Stephen W Davies 2018

Stephen W Davies 2018

New techniques used to link function and connectivity: Towards the
complete functional connectome
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21848-53.

45

SWD UCL 2017

(A) Adult D1R-Cre or D2R-Cre mice are injected in the dorsal striatum with 180 nl of AAV9 expressing TVA and rabies
glycoprotein in a Cre-dependent manner.

(B) 21 days later, the same mice are injected with 180 nl of monosynaptic rabies virus that can only infect cells
expressing TVA, and can only spread retrogradely from cells expressing rabies glyco- protein.

(C) Direct inputs onto either direct pathway (D1R- expressing) or indirect pathway (D2R-expressing) MSNs are labeled
one week after rabies injection7 SWD UCL 2017
Neuron. 2013 Jul 24;79(2):347-60.

SWD UCL 2017

SWD UCL 2017
Nature Neuroscience 14 527-532 (2011)
NATURE METHODS | VOL.10 NO.6 | JUNE 2013 | 515