Anatomy of the basal ganglia. Dana Cohen Gonda Brain Research Center, room 410

Transcription

1 Anatomy of the basal ganglia Dana Cohen Gonda Brain Research Center, room 410

2 The basal ganglia The nuclei form a small minority of the brain s neuronal population. Little is known about their function in the normal state despite many years of study. The basal ganglia receive projections from most cortical areas The basal ganglia project out to cortical areas involved in the generation of behavior Act in parallel with other output systems of the cortex and thus may not play a primary role in generating behavior Many neurological disorders are associated with their malfunction. Essential for several types of learning

3 Neurological disorders Motor Parkinson s disease Huntington s disease Dystonia (sustained muscle contractions cause twisting and repetitive movements or abnormal postures) Tourette s syndrome Behavioral Obsessive-compulsive disorder (OCD) Attention deficit hyperactivity disorder (ADHD)

4 The cortico-basal ganglia circuits consist of: Neocortex The striatum (caudate - putamen and the core of nucleus accumbens) The globus pallidus (GP) (lateral and medial) The subthalamic nucleus (STN) Substantia nigra (SN) (pars compacta and pars reticulata) and the ventral tegmental area (VTA)

5 Anterior to posterior coronal view

6 Anterior to posterior coronal view

7 Anterior to posterior coronal view

8 Input and output of the basal ganglia Cortex to striatum: glutamate MGP and SNr: GABA

9 Cortical input to the striatum originates from most cortical areas Primary and higher order sensory areas, motor, premotor, and prefrontal regions, and limbic cortical areas. The input is organized topographically Frontal areas project to rostral striatum Sensorimotor cortex projects to dorsolateral striatum Parietal cortex projects to caudal striatum Highly interconnected cortices may overlap in the striatum Numbers: There are 17 million cortico-striatal cells There are almost 2.8 million striatal projection neurons No 2 striatal neurons share their cortical input

10 The striatum The major input nucleus of the BG. Made up of the putamen, the caudate nucleus and nucleus accumbens which have similar histological and anatomical characteristics. Receive input from most of the cortex (and the thalamus) Complex bidirectional interaction with the substantia nigra pars compacta (SNc) Output to both segments of the globus pallidus (GP) & the substantia nigra pars reticulata (SNr)

11 Striatum Medium Spiny Neurons I MSNs = Medium Spiny Neurons > 90% of all cells in striatum >10,000 cortical inputs to one MSN GABAergic projection neurons Dense collateral network Two states: down state with low resting potential and no firing up state characterized by short firing episodes.

12 Striatum Medium Spiny Neurons II MSNs are typically quiet with no baseline firing. Sensory and movement related response comprises of a short high frequency burst. Highly specific to portion of the task and parts of the movement but can respond to several events. Affected by sequence context or reward contingency.

13 The interneurons of the striatum make up about 5-10% of the neurons TANs: large aspiny neurons Ach (Was previously thought to be the projection neuron)

14 The GABAergic interneurons of the striatum FSNs: medium aspiny neurons that contain parvalbumin Medium aspiny neurons that contain somatostatin

15 The medial globus pallidus and the SNr Primarily made up of GABAergic projection neurons. Firing rate at rest is spikes/s and is highly irregular (The ultimate Poissonian neuron). Sensory and motor response is broad and includes increases and decreases of firing rate.

16 The lateral globus pallidus (GPe) Same morphology as the MGP High frequency pausers (HFP) & lowfrequency bursters (LFB) Internal to the basal ganglia with no external connections for input or output

17 The subthalamic nucleus Made up mainly of projection neurons. Firing rate at rest is spikes/s with short burst following movement. The projection neurons are glutamatergic and send their output to the GPi & SNr. In addition to its role in the indirect pathway, has direct cortical inputs forming the hyperdirect pathway.

18 Direct and indirect pathways The direct pathway causes disinhibition The indirect pathway is more complex but likely to counterbalance the direct pathway

19 Components of the indirect pathway

20 Feedback pathways

21 Dual projections in the basal ganglia

22 Synaptic inputs to the SNr The SNc and SNr cannot be distinguished based on the morphological properties of the neurons Dopaminergic neurons GABAergic neurons

23 The striatum is organized in cell clusters (striosomes or patches) in a background of lesser cellular density (matrix). MSNs in the patch and matrix project to different parts of the SN They receive inputs from all cortical regions

24 The action selection hypothesis Striatal neurons act as coincidence detectors using their binary like activation. Lateral inhibition leads to a winner/s take all within the striatum. Striatal activation is summed linearly in the GPi leading to its inhibition. This in turn leads to disinhibition of the correct action within the thalamus & finally the cortex.

25 The focusing hypothesis Direct vs. Indirect Pathways Direct Pathway: Causes pauses in GPi, facilitating the correct movement. Indirect Pathway: Causes increases in GPi firing, leading to surround inhibition, suppress competing movements. 70% of movement-related changes in GPi are increases

26 Direct and indirect striatal projection neurons selectively express the D1 and D2 receptors

27 Inputs to the proximal and distal dendrites of the MSNs

28 The balance between the pathways Dopamine binds to two receptor families D1 & D2 which are expressed preferentially on neurons of the direct & indirect pathway respectively. Dopamine facilitates D1 receptors and inhibits D2 receptors. Direct pathway - positive feedback loop Cortex (+) Striatum (-) GPi (-) Thalamus (+) Cortex Indirect pathway negative feedback loop Cortex (+) Striatum (-) GPe (-) STN (+) GPi(-) Thalamus (+) Cortex

29 The Box and Arrow model: Normal activity Cortex Indirect pathway D2 Striatum SNc D1 Direct pathway GPe Thalamus STN Basal Ganglia GPi/SNr excitatory inhibitory

30 The Box and Arrow model: Parkinson s Disease Cortex D2 Indirect pathway Striatum SNc D1 Direct pathway GPe Thalamus STN Basal Ganglia GPi/SNr excitatory inhibitory

31 The classical view of the basal ganglia holds that there are parallel functional circuits in the organization of the basal ganglia with considerable interaction between adjacent circuits